Leishmaniasis, sleeping sickness (Human African Trypanosomiasis), Chagas disease (American Trypanosomiasis) and malaria are tropical parasitic diseases responsible for high mortality and morbidity each year in low-income countries. Due to the lack of vaccines and of safe, effective and affordable treatments, there is an urgent need to reinforce the existing therapeutic arsenal against these killers. One of the main opportunities is through the discovery of new molecules from natural origin. The gaps identified in the R process aiming to deliver new medicines for neglected diseases however also apply to natural products. A key review of the most promising antiprotozoal molecules recently discovered from natural resources is presented here together with a critical update on their current development status.