In areas of intense Plasmodium falciparum transmission, pregnancies are associated with substantial malaria-related morbidity and mortality. The mechanisms of protection against malaria are not fully understood. Protective immunity is acquired during childhood. Until recently, it has been poorly understood why the clinical protection against malaria is rendered inefficient when young women become pregnant. Over the last century, the epidemiology of pregnancy associated P. falciparum malaria has been the subject of numerous research articles with excellent reviews of this literature published.1–4 However, most of these reviews focus on the mounting evidence that protective immunity to pregnancy-associated malaria depend on acquisition of antibodies directed against parasite-encoded variant antigens on the surface of the infected red blood cells and only one gives attention on the “cortisol hypothesis.”2 This review will illustrate the cortisol hypothesis, and because natural killer (NK) cells play a crucial role in this hypothesis, an update on NK cell function and biology is provided in order to better understand the role of NK cells in the susceptibility of pregnant women to malaria.