Malaria remains a deadly parasitic disease caused by Plasmodium, claiming almost half a million lives every year. While parasite genetics and biology are often the major targets in many studies, it is becoming more evident that host genetics plays a crucial role in the outcome of the infection. Similarly, Plasmodium infections in mice also rely heavily on the genetic background of the mice, and often correlate with observations in human studies, due to their high genetic homology with humans. As such, murine models of malaria are a useful tool for understanding host responses during Plasmodium infections, as well as dissecting host-parasite interactions through various genetic manipulation techniques. Reverse genetic approach such as quantitative trait loci studies and random mutagenesis screens have been employed to discover novel host genes that affect malaria susceptibility in mouse models, while other targeted studies utilize mouse models to validate observation from human studies. Herein, we review the findings from the past and present studies on murine models of hepatic and erythrocytic stages of malaria and speculate on how the current mouse models benefit from the recent development in CRISPR/Cas9 gene editing technology.