An understanding of how the cell cycle is controlled, and how the complex controls that govern entry into and exit from the cell cycle work are reviewed in brief in this article. Cell cycle controlling mechanism is essential, considering this cycle is cell’s program for growth and development. Progression through the cell cycle is controlled by a group of kinases called cyclin-dependent kinases (CDK) which are thought to phosphorylate cellular substrate, such as the retinoblastoma (Rb) gene in Rb pathway that are responsible for progression into each of the phases of cell cycle. Rb pathways is one of the cell cycle controlling mechanisms, especially from G1 to S phase, where transcription and protein synthesis occur. Rb controlling mechanism is through binding to transcription factor group E2F. Rb forms HDAC-Rb-E2F complex to inhibit transcription. Rb plays an important role to form the complex, so that the transcription does not occur indefinitely. Conversely, in order for the cell cycle to progress to the next phase, the complex has to be broken by phosphorylation of Rb. Cyclin D-CDK 4/6 complex phosphorylates Rb so as to improve HDAS. Cyclin D-CDK 4/6 complex functions to remove E2F from Rb. Cyclin activity itself is regulated by CKI which functions at proliferation, checkpoint control and tumor suppressor. Overexpression of cyclin-CDK complex and CKI function disruption lead to uncontrollable Rb activities. Imperfect cell cycle controlling mechanism will cause cells with DNA damage to complete the cell cycle and become mutated cells. The mutated cells will lead to various disorder, such as cancer.