In 1993, Malawi became the first African country to replace chloroquine with sulfadoxine-pyrimethamine nationwide in response to high rates of chloroquine-resistant falciparum malaria. To determine whether withdrawal of chloroquine can lead to the reemergence of chloroquine sensitivity, the prevalence of the pfcrt 76T molecular marker for chloroquine-resistant Plasmodium falciparum malaria was retrospectively measured in Blantyre, Malawi. The prevalence of the chloroquine-resistant pfcrt genotype decreased from 85% in 1992 to 13% in 2000. In 2001, chloroquine cleared 100% of 63 asymptomatic P. falciparum infections, no isolates were resistant to chloroquine in vitro, and no infections with the chloroquine-resistant pfcrt genotype were detected. A concerted national effort to withdraw chloroquine from use has been followed by a return of chloroquine-sensitive falciparum malaria in Malawi. The reintroduction of chloroquine, ideally in combination with another antimalarial drug, should be considered in areas where chloroquine resistance has declined and safe and affordable alternatives remain unavailable.