Almost all the drugs that are widely used today against Plasmodium spp., the causative agent of malaria, target the asexual blood stages of the parasite. Widespread drug resistance severely restricts our ability to control malaria and makes it necessary to seek novel antimalarial compounds. Here, we advocate the development of true causal chemoprophylactic drugs that will fully inhibit the obligate short-lived hepatic forms that precede blood infections. Such drugs will prevent pathology and interrupt transmission, and could therefore have an important role in the control of malaria and its eventual eradication.