Protein kinase C (PKC) represents a family of phospholipid-dependent serine / threonine kinase. PKC was detected in almost all types of cells and tissues in the body. The activation of PKC is involved in the signal regulation of many physiological and pathological processes. PKC has multiple isoforms (α;, βI, βII, γ, δ, ε, η, θ, ξ, ι and μ). PKC-mediated cellular processes are tissue- and isoform-specific. Investigations on selective or isoform-specific PKC inhibitors have attracted great attention during last two decades. Recent studies demonstrated that LY333531, a PKC-β-specific inhibitor, reduced the development of diabetic vascular complications in animal models and prevented hyperglycemia-induced impairment of endothelialdependent vasodilation in healthy subjects. Results from phase I clinical trial suggested low risk of the inhibitor. Phase III clinical trials on the safety and the preventive effects of the PKC-β-specific inhibitor on diabetic complications are under progress. The efficacy of ISSI-3521, a PKC-α antisense inhibitor, on slowing the growth and metastasis of solid tumors is currently being examined in clinical trials. Partial responses in the prevention of the progress of malignancies were found in early phases of clinical trials for UCN-01 and CGP41251, two partially isoform-specific PKC inhibitors. Recent findings suggest that isoform-specific PKC inhibitors are potentially beneficial to the prevention or treatment of some common diseases, including cancers and diabetic vascular complications. Safety and efficacy studies of the PKC inhibitors will be required through large-scale long-term clinical trials.