The POU domain transcription factors have been proposed to be important regulators of key developmental processes. The characterization of naturally occurring mutations and targeted gene deletions has demonstrated that many of these proteins function in terminal differentiation events, including lineage determination, migration, proliferation, survival, and maintenance of mature cell types. POU domain factors can exert critical functions in cell types in which they exhibit either transient or sustained expression patterns, and it is likely that their target genes encode receptors, guidance molecules, and neuropeptides that define differentiated phenotypes.