Although the last two decades have seen a substantial decline in malaria incidence and mortality due to the use of insecticide-treated bed nets and artemisinin combination therapy, the threat of drug resistance is a constant obstacle to sustainable malaria control. Given that patients can die quickly from this disease, public health officials and doctors need to understand whether drug resistance exists in the parasite population, as well as how prevalent it is so they can make informed decisions about treatment. As testing for drug efficacy before providing treatment to malaria patients is impractical, researchers need molecular markers of resistance that can be more readily tracked in parasite populations. To this end, much work has been done to unravel the genetic underpinnings of drug resistance in Plasmodium falciparum. The aim of this review is to provide a broad overview of common genomic approaches that have been used to discover the alleles that drive drug response phenotypes in the most lethal human malaria parasite.