Members of the protein kinase C family respond to second messengers and are involved in controlling a broad array of cellular functions. The overlapping specificity and promiscuity of these proteins has promoted the view that specific binding proteins constrain individual family members to create the appropriate specificity of action. It is speculated that such protein kinase C–regulator protein interactions affect substrate availability as well as exposure to allosteric activator(s) and that consequent interactions specify cellular location and impose integration with other signaling systems. These predicted features have been realized in the identification of many protein kinase C interacting proteins and examples of these are discussed. BioEssays 22:245–254, 2000. © 2000 John Wiley & Sons, Inc.