Plasmodium vivax is the most widespread human malaria parasite, but has received much less attention than Plasmodium falciparum during the past 50 years of research. Plasmodium vivax was historically seen as causing only benign disease, but this view has recently changed, with increased recognition of the burden of vivax malaria, as well as numerous case reports of severe malaria or death caused by this parasite. The complexity of P. vivax biology is characteristic of specific features of the parasite, and recent years have seen major progress in our understanding of this complexity. In this review, we analyze the latest advances in the field, describing the constraints that the unique features of P. vivax place on drug treatments aimed at controlling or eliminating it.