Antivenom is an effective treatment of snakebite but, because of the complex interplay of fiscal, epidemiological, therapeutic efficacy and safety issues, the mortality of snakebite remains unacceptably high. Efficiently combating this high level of preventable death amongst the world's most disadvantaged communities requires the globally-coordinated action of multiple intervention programmes. This is the overall objective of the Global Snakebite Initiative. This paper describes the challenges facing the research community to develop snakebite treatments that are more efficacious, safe and affordable than current therapy.