The p21-activated kinases (PAKs) are signaling nodes that play a crucial role in cellular processes including cell motility, differentiation, survival, gene transcription, and hormone signaling. PAKs are highly conserved family of serine-threonine kinases that act as effector for small GTPases Rac and Cdc42. Most of our knowledge about PAK functions has been derived from genetic approaches in lower organisms and many of these functions are similar to that seen in mammalian cells. In this review, we have summarized the extensive information generated in lower eukaryotes and very briefly discussed the current status of PAKs in humans. © 2009 Wiley-Liss, Inc.