Unfinished business: target-based drug discovery.

The switch in the mid-1980s/early 1990s from a phenotypic approach to a target-based approach to drug discovery has been followed by low productivity of new drugs entering the market. Reasons for the (necessary) switch and unsolved problems with both approaches to drug discovery are discussed. The S-curve theory of new technology development and introduction can act as guide as to when an upturn in productivity can be expected; this should occur during the next decade leading possibly to a new golden age of drug discovery.