In the US, two antivenins are marketed for the treatment of snake envenomation. The horse-derived serum-globulin-based Antivenin (Crotalidae) Polyvalent (ACP) has been available since 1954. There are few data on the efficacy and incidence of adverse events that occur following the administration of ACP. Most of the data are retrospective, anecdotal, or case reports. In 2000, ovine-derived serum-globulin-based ACP (Crofab) became available. Crofab is said to cause fewer reactions than ACP, but there are few comparative data to substantiate this claim. Although both antivenins ameliorate the systemic symptoms following snake envenomation, the efficacy of either antivenin in decreasing oedema and swelling is unknown for a number of reasons. Clinical trials are small and have not included control arms. The degree of oedema, as well as the efficacy of the antivenin in decreasing oedema, may depend on the genera of the snake (usually unknown) that envenomated the patient. This article compares available data on clinical aspects of the two antivenins. More prospective data are needed to determine the comparative efficacy of the two antivenins, or the efficacy of Crofab in preventing tissue oedema. There are still unanswered questions regarding the optimal dosing regimen of Crofab.