Drug resistance in malarial parasites is arguably the greatest challenge currently facing infectious disease research. In addressing this problem, researchers have been intrigued by similarities between drug-resistant malarial parasites and tumour cells. For example, it was originally thought that the role of pfMDR (Plasmodium falciparum multidrug resistance) proteins was central in conferring antimalarial multidrug resistance. However, recent work has questioned the precise role of MDR proteins in multidrug resistance. In addition, recent ground-breaking work in identifying mutations associated with antimalarial drug resistance might have led to identification of yet another parallel between drug-resistant tumour cells and malarial parasites, namely, intriguing alterations in transmembrane ion transport, discussed here by Paul Roepe and James Martiney. This further underscores an emerging paradigm in drug-resistance research.