The tetratricopeptide repeat (TPR) motif is a protein‐protein interaction module found in multiple copies in a number of functionally different proteins that facilitates specific interactions with a partner protein(s). Three‐dimensional structural data have shown that a TPR motif contains two antiparallel α‐helices such that tandem arrays of TPR motifs generate a right‐handed helical structure with an amphipathic channel that might accommodate the complementary region of a target protein. Most TPR‐containing proteins are associated with multiprotein complexes, and there is extensive evidence indicating that TPR motifs are important to the functioning of chaperone, cell‐cycle, transcription, and protein transport complexes. The TPR motif may represent an ancient protein‐protein interaction module that has been recruited by different proteins and adapted for specific functions. BioEssays 1999;21:932–939. © 1999 John Wiley & Sons, Inc.