The biological function of protein kinase C (PKC) depends on its catalytic activity and spatial localization. Its catalytic competence and localization in the resting state are regulated by serine/threonine phosphorylations, i.e., "maturation." Upon stimulation of various receptors, PKC is catalytically activated by several activators including diacylglycerol. In addition, PKC often translocates to particular subcellular compartments including the plasma membrane and Golgi complex, and such translation is here referred to as "targeting." In short, the physiological function of PKC is controlled by the three events: maturation, catalytic activation, and targeting. Catalytic activation and targeting contribute to temporal, spatial, and isotype-specific regulation of PKC. This review summarizes the evidence for the role of these three events in the isotype-specific activation of PKC, with particular emphasis on catalytic activation and targeting by lipid mediators.