Protein kinase C has been in the spotlight since the discovery two decades ago that is activated by the lipid second messenger diacylglycerol. Despite protein kinase C's enduring stage presence, the regulation and specific roles of its isozymes in defined cellular processes are still under intense investigation. Elucidation of the structures of protein kinase C's regulatory modules, the discovery that phosphorylation regulates the enzyme, and the identification of targeting mechanisms have made the past year a significant one for unveiling how this ubiquitous class of enzymes operates.