Resistance to currently used drugs is a serious problem in most fields of antimicrobial chemotherapy. Crossresistance between two of the major classes of drug used in the treatment of African trypanosomiasis, the melaminophenyl arsenicals and diamidines is easily selected in the laboratory. Here, Mike Barrett and Alan Fairlamb outline the mechanism underlying this crossresistance, which appears to arise as a result of alterations in an unusual adenosine transporter involved in the uptake of these drugs.