Malaria is a disease transmitted to humans through female mosquito bites. The disease is caused by a parasite that advances through a complex life cycle composed of unique stages depending on its changing host environments. Millions of people, primarily inhabitants of Africa and Southeast Asia, succumb to the disease every year. In the past few decades, there has been a rise in resistance to current antimalarial therapies, sounding the alarm for intervention. Chloroquine, sulfadoxine-pyrimethamine, and artemisinin-based combination therapies are among the most potent pharmacological tools against the parasite, but mutations in P. falciparum have begun to disarm these drugs. This review summarizes mechanisms of action for various antimalarial drugs and carefully examines the genetic mutations in Plasmodium falciparum conferring drug resistance.