Cancer has continued to be utmost challenging and life-threatening diseases to treat. Worldwide, cancer has been proven to be a major cause of death after cardiovascular diseases. The development of new drugs that can be able to inhibit the proliferation of cancerous cells only with minimum or without any side effects on healthy cells is a quite challenging task. Protein kinases are enzymes located in the cytoplasm that phosphorylate proteins. Protein kinases mediate most of the signal transduction in eukaryotic cells and also control many other cellular processes, including metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, development, the immune response, nervous system function, apoptosis, and differentiation. Normally, the activity protein kinases are stringently regulated. However, under pathological conditions, deregulation of protein kinases can lead to altered kinase expression and functions, and the initiation and survival of tumors. Therefore, protein kinases are a very attractive target class for therapeutic interventions in many disease states such as cancer. Kinase inhibitors now account for a quarter of all current drug discovery research and development efforts. Therefore, researchers around the globe are involved in the development of more efficient and safer targeted kinase inhibitors. ObjectivesTo complement the published literature on clinical kinase inhibitors, we have prepared a review that recaps this large data set into an accessible format for the medicinal chemistry community. Here, we review the remarkable progress made over the past 20 years in improving the potency and specificity of small-molecule inhibitors of protein for cancer therapy. ResultsIn summary, the potential for developing novel types of kinase inhibitor is huge, and we confidently predict that this will continue to be a major growth area over the next 20 years,