Malaria continues to affect public health and economic growth in many regions of the world. The number of infections continues to rise and is associated with increased mortality, despite basic science and public health efforts. Drug therapy remains the mainstay of treatment and prevention of this disease. Plasmodium has a complex life cycle involving an arthropod vector and distinct stages within the human host. Each parasite stage plays a unique role in transmission, disease, and latency. These different stages may vary in their response to the various antimalarial compounds. This article will review antimalarial therapies and drug resistance in the context of the parasites' biology.