Members of the protein kinase C (PKC) family play central roles in a number of important signal transduction pathways and are attractive targets in drug development for various diseases. Because of the high level of homology among its members, designing isozyme-specific PKC inhibitors has been extremely challenging. A recent patent application from the Albert Einstein College of Medicine describes a novel method by combinatorial modification of the substrate consensus sequences of an individual PKC isozyme. This approach has led to the identification of potent and isozyme-selective peptide inhibitors of PKCα, PKCδ and PKCζ.