Signal transduction is essential for life. In living cells, several signal transduction pathways interact with each other to form complicated signal network. Second messengers, such as Ca2+, cAMP and cGMP, play fundamental roles in the cellular responses via binding to their target proteins. Recent advances in signal transduction research enables us to design more specific and selective inhibitors of a certain signaling molecule or pathway. Specific inhibitors (molecular probes) of the signal transduction pathway, once identified, will be of vital importance to pharmacological intensive experiments, and also to clinical applications, that is “signal transduction therapy”. For example, Ca2+/ calmodulin-dependent protein kinases (CaM kinases) are involved in a variety of cell functions including regulation of gene expression and cell cycle via phosphorylation of CREB and cdc25 (a p34cdc2 phosphatase), respectively. Furthermore, a derivative of CaM kinases inhibitors has been proved to be clinically available. Pharmacological and molecular biological approaches on protein kinases will become more and more powerful strategy not only to investigate the signal transduction systems but to create novel remedies. The first aim of this presentation is to highlight recent findings in Ca2+ signaling. The other aim is to discuss the usefulness of specific protein kinase inhibitors (KN-62 and its derivatives), with introducing the first example of “Signal transduction therapy”.