Rational drug-screening strategies have been limited by the number of avail
able protein targets, The fields of genomics and functional genomics are no
w merging into 'chemical genomics' approaches, in which large numbers of po
tential target proteins can be used in standardized high-throughput drug-sc
reening assays, Because protein-protein interactions are critical to most b
iological processes and can be tested in standardized assays, they may repr
esent optimal targets in the chemical-genomics era. The reverse two-hybrid
system appears to have several properties that would be critical for the su
ccess of this approach.