There is a lack of effective, safe, and affordable pharmaceuticals to control infectious diseases that cause high mortality and morbidity among poor people in the developing world. We analysed outcomes of pharmaceutical research and development over the past 25 years, and reviewed current public and private initiatives aimed at correcting the imbalance in research and development that leaves diseases that occur predominantly in the developing world largely unaddressed. We compiled data by searches of Medline and databases of the US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products, and reviewed current public and private initiatives through an analysis of recently published studies. We found that, of 1393 new chemical entities marketed between 1975 and 1999, only 16 were for tropical diseases and tuberculosis. There is a 13-fold greater chance of a drug being brought to market for central-nervous-system disorders or cancer than for a neglected disease. The pharmaceutical industry argues that research and development is too costly and risky to invest in low-return neglected diseases, and public and private initiatives have tried to overcome this market limitation through incentive packages and public-private partnerships. The lack of drug research and development for "non-profitable" infectious diseases will require new strategies. No sustainable solution will result for diseases that predominantly affect poor people in the South without the establishment of an international pharmaceutical policy for all neglected diseases. Private-sector research obligations should be explored, and a public-sector not-for-profit research and development capacity promoted.