Antivenoms can be classified into monovalent (when they are effective against a given species’ venom) or polyvalent (when they are effective against a range of species, or several different species at the same time). The first antivenom for snakes (called an anti-ophidic serum) was developed by Albert Calmette, a French scientist of the Pasteur Institute working at its Indochine branch in 1895, against the Indian Cobra (Naja naja). Vital Brazil, a Brazilian scientist, developed in 1901 the first monovalent and polyvalent antivenoms for Central and South American Crotalus, Bothrops and Elaps genera, as well as for certain species of venomous spiders, scorpions, and frogs. They were all developed in a Brazilian institution, the Instituto Butantan, located in São Paulo, Brazil.

Antivenoms for therapeutic use are often preserved as freeze-dried ampoules, but some are available only in liquid form and must be kept refrigerated. (They are not immediately inactivated by heat, so a minor gap in the cold chain is not disastrous.) The majority of antivenoms (including all snake antivenoms) are administered intravenously; however, stonefish and redback spider antivenoms are given intramuscularly. The intramuscular route has been questioned in some situations as not uniformly effective.

Antivenoms bind to and neutralize the venom, halting further damage, but do not reverse damage already done. Thus, they should be administered as soon as possible after the venom has been injected, but are of some benefit as long as venom is present in the body. Since the advent of antivenoms, some bites which were previously invariably fatal have become only rarely fatal provided that the antivenom is administered soon enough.

Antivenoms are purified by several processes but will still contain other serum proteins that can act as antigens. Some individuals may react to the antivenom with an immediate hypersensitivity reaction (anaphylaxis) or a delayed hypersensitivity (serum sickness) reaction and antivenom should, therefore, be used with caution. Despite this caution, antivenom is typically the sole effective treatment for a life-threatening condition, and once the precautions for managing these reactions are in place, an anaphylactoid reaction is not grounds to refuse to give antivenom if otherwise indicated. Although it is a popular myth that a person allergic to horses “cannot” be given antivenom, the side effects are manageable, and antivenom should be given as rapidly as the side effects can be managed.

Sheep are generally used in preference over horses now, however, as the potential for adverse immunological responses in humans from sheep-derived antibodies is generally somewhat less than that from horse-derived antibodies. The use of horses to raise antibodies – in Australia at least, where much antivenom research has been undertaken (by Sutherland and others for example) – has been attributed to the research base originally having been a large number of veterinary officers. These vets had, in many cases, returned from taking part in the Boer and First World Wars and were generally experienced with horses due to working with cavalry. The large animal vets were similarly oriented given the use of horses as a prime source of motive power and transport, especially in the rural setting. The overall experience with horses naturally made them the preferred subject in which to raise antibodies. It was not until later that the immuno-reactivity of certain horse serum proteins was assessed to be sufficiently problematic that alternatives in which to raise antibodies were investigated.

In the U.S. the only approved antivenom for pit viper (rattlesnake, copperhead and water moccasin) snakebite is based on a purified product made in sheep known as CroFab. It was approved by the FDA in October, 2000. U.S. coral snake antivenom is no longer manufactured, and remaining stocks of in-date antivenom for coral snakebite expired in the Fall of 2009, leaving the U.S. without a Coral snake antivenom. Efforts are being made to obtain approval for a coral snake antivenom produced in Mexico which would work against U.S. coral snakebite, but such approval remains speculative. In the absence of antivenom, all coral snakebite should be treated in a hospital by elective endotracheal intubation and mechanical ventilation until the effects of coral snake neurotoxins abate. It is important to remember that respiratory paralysis in coral snakebite can occur suddenly, often up to 12 or more hours after the bite, so intubation and ventilation should be employed in anticipation of respiratory failure and not after it occurs, when it may be too late.
Natural and acquired immunity

Although individuals can vary in their physiopathological response and sensitivity to animal venoms, there is no natural immunity to them in humans. Some ophiophagic animals are immune to the venoms produced by some species of venomous snakes, by the presence of antihemorrhagic and antineurotoxic factors in their blood. These animals include King snakes, opossums, mongooses, and hedgehogs.

It is quite possible to immunize a person directly with small and graded doses of venom rather than an animal. According to Greek history, King Mithridates did this in order to protect himself against attempts of poisoning, therefore this procedure is often called mithridatization. However, unlike a vaccination against disease which must only produce a latent immunity that can be roused in case of infection, to neutralize a sudden and large dose of venom requires maintaining a high level of circulating antibody (a hyperimmunized state), through repeated venom injections (typically every 21 days). The long-term health effects of this process have not been studied. For some large snakes, the total amount of antibody it is possible to maintain in one human being is not enough to neutralize one envenomation[citation needed]. Further, cytotoxic venom components can cause pain and minor scarring at the immunization site. Finally, the resistance is specific to the particular venom used; maintaining resistance to a variety of venoms requires multiple monthly venom injections. Thus, there is no practical purpose or favorable cost/benefit ratio for this, except for people like zoo handlers, researchers, and circus artists who deal closely with venomous animals. Mithridatization has been tried with success in Australia and Brazil and total immunity has been achieved even to multiple bites of extremely venomous cobras and pit vipers. Starting in 1950, Bill Haast successfully immunized himself to the venoms of Cape, Indian and King cobras.

Because neurotoxic venoms must travel farther in the body to do harm and are produced in smaller quantities, it is easier to develop resistance to them than directly cytotoxic venoms (such as those of most vipers) that are injected in large quantity and do damage immediately upon injection.