Whilst significant numbers of new hit molecules have been identified against the asexual stages of Plasmodium falciparum (Pf) in the past 10 years, fewer than anticipated have progressed. Alternative strategies to identify additional distinctly different chemotypes directed at new targets are therefore under investigation. Re-evaluation of the assays currently used and their potential limitations or bias is essential. The inclusion of additional activity across multiple Pf life cycle stages for new lead compounds has lead to the development of assays which enable extensive characterisation. To determine whether different chemotypes could be identified if primary screening was undertaken against a stage other than the asexual stages, ~ 100K compound collection was screened against late stage Pf gametocytes. The outcomes will be discussed.