Problems associated with the current therapies of sleeping sickness include toxicity, resistance and a lack of a guaranteed supply. However, no new formulations are close to gaining a licence for clinical use and relatively few compounds have been shown to be effective in experimental systems. Many potentially good biochemical targets for drugs have been identified. Some of these have been validated and lead compounds have been developed. However, the biology of trypanosomes means that various pharmacological demands must be met in developing new trypanocides for clinical use. Foremost among these problems is the blood-brain barrier, across which trypanocides must cross to reach parasites in the cerebrospinal fluid.The principal problem, however, relates not to biological difficulties, which are technically surmountable, but to economics. Put simply, most representatives of the pharmaceutical industry believe that selling drugs to the victims of sleeping sickness will not yield sufficient income to justify expenses needed for the development of novel reagents. Only when this economic barrier can be lowered will new drugs emerge for use against sleeping sickness.