The three trypanocides used to control tsetse-transmitted trypanosomiasis in domestic animals in Africa have been in use for over 40 years and, not surprisingly, resistance of trypanosomes to these drugs has emerged. Because of the relatively limited market in Africa and the high costs of developing and licensing new drugs, international pharmaceutical companies have shown little interest in the development of new trypanocides for use in either animals or humans. Therefore, the current challenge is to achieve optimal use of the relatively old existing drugs, and it is in this context that the problem of drug resistance has to be quantified – as discussed here by Stanny Geerts, Peter Holmes, Oumar Diall and Mark Eisler.