As the major threat of poor renal outcome and survival quality, the mechanism of acute kidney injury (AKI) progressing to chronic kidney disease (CKD) has aroused much attention. The cell cycle arrest, one of the major culprits, accelerates the AKI-to-CKD transition through maladaptive repair that involved overwhelming cytokines excretion and inflammation storm, epithelial-mesenchymal transition, organelles stress/crosstalk, aging activation as well as peritubular capillary rarefaction. Therefore, the cell cycle regulation can serve as a novel potential therapeutic target for the prevention, alleviation and even interruption of AKI -to- CKD transition.