Tyrosine kinases have emerged as important tumor targets for the design of potent and selective inhibitors. Eighteen of these tyrosine kinase inhibitors (TKIs) have already been approved for the treatment of diseases that were previously essentially resistant to standard chemotherapy. Major efforts are ongoing that focus on the development of companion diagnostics for investigational and approved TKIs, as well as on integrating clinical pharmacology principles in clinical practice to decrease toxicity and improve efficacy.