It is well known that cyclins and cyclin-dependent kinases (CDKs) play essential roles in regulation of the cell cycle. In past two decades, the scientific researches suggest that the cyclin D1/ CDK4 complex is a key regulator of the transition through the G1 phase of the cell cycle. Moreover, deregulation of the cyclin D /CDK4 pathway has been identified in multiple tumor types. Thus, CDK4 is a genetically validated therapeutic target; hence, there has been a surge of interests in finding selective CDK4 inhibitors as anti-cancer agents. This review will give the recent progress in the studies of structure, functions of CDK4 and highly selective and potent CDK4 inhibitors.