This paper examines the cultural interpretations and the perceived efficacy and side effects of antimalarials in Tanzania. Interviews with 56 mothers of children diagnosed with malaria revealed that they were nostalgic about chloroquine, a banned antimalarial. Additional findings indicated that a majority of the mothers had an overall negative disposition toward sulfadoxine-pyrimethamine (SP), the first-line antimalarial. Mothers considered the persistence of fever as the primary undesirable side effect of SP, while also mentioning a range of other side effects. Mothers who could not afford an alternative to SP, rationalized the drug's side effects as indicative of disease egress. It is argued that ethnographic studies of cultural perceptions of malaria and antimalarials provide useful perspectives on how people negotiate the identity of a febrile illness, and how they understand and interpret the efficacy of existing antimalarials. In acknowledging the intra-cultural variability in perceptions of malaria and antimalarials, health policy makers must be cautious when implementing a 'one drug fits all' approach to malaria control.