Snakebite envenoming is responsible for as many as 138 000 deaths annually, making it the world's most lethal neglected tropical disease (NTD). There is an urgent need to improve snakebite treatment, which currently relies on outdated and poorly tolerated biologic antivenoms that are often weakly efficacious, must be given intravenously in a healthcare setting, and are expensive to those who need them the most. Herein we describe the challenges associated with the discovery and development of new snakebite treatments and detail the great potential of venom toxin-inhibiting small molecule drugs. We finish by highlighting successful enabling strategies applied to other NTDs that could be exploited to facilitate the development of next-generation small molecule-based snakebite treatments.