Malaria is a major infectious disease worldwide, with over 1 million deaths in African children every year. The molecular pathways of pathogenesis of the Plasmodium parasite and the host mechanisms of defense against this infection remain poorly understood. Epidemiological studies, together with linkage analyses in endemic areas have clearly pointed at a genetic component of innate susceptibility and severity of disease. In humans, this genetic trait is complex, and has been studied in a mouse experimental model over the past few years. Inbred strains of mice show different degrees of susceptibility to infection with Plasmodium chabaudi, and the genetic component of these inter-strain differences has been studied in standard informative backcross and F2 populations, as well as in recombinant inbred strains and more recently, in recombinant congenic strains. These studies have shown that genetic susceptibility to malaria is also complex in mice, and have led to the mapping of major susceptibility Char (Chabaudi resistance) loci, located on chromosomes 9 (Char1), 8 (Char2), 17 (Char3) and 3 (Char4).