The cell cycle is a tightly regulated process that ensures accurate DNA replication and chromosome segregation. This review focuses on the mechanisms that control the cell cycle, including the regulation of cyclin-dependent kinases (CDKs) by cyclins and CDK inhibitors, as well as the role of phosphorylation events. The complexity of cell cycle regulation is reflected in the various alterations leading to uncontrolled cell proliferation and cancer development. Targeting the cell cycle, particularly CDKs, presents unique opportunities for drug discovery. The review discusses different families of CDK inhibitors that act through ATP competition, with at least three compounds (flavopiridol, UCN-01, roscovitine) currently in clinical trials. The regulation of the cell cycle involves multiple checkpoints, such as the G1/S and G2/M checkpoints, which ensure the integrity of DNA and the proper alignment of chromosomes during mitosis. Mutations in genes encoding CDKs, cyclins, CDK-activating enzymes, CDK inhibitors, and checkpoint proteins are common in cancer, leading to deregulation of the cell cycle. The review also highlights the development of CDK inhibitors as potential anticancer drugs, including purine analogues, plant cytokinin analogues, pyrimidine analogues, butyrolactones, flavonoids, paullones, indolinones, and other non-specific CDK inhibitors. These inhibitors have shown promise in preclinical studies and clinical trials, offering new therapeutic options for cancer treatment.The cell cycle is a tightly regulated process that ensures accurate DNA replication and chromosome segregation. This review focuses on the mechanisms that control the cell cycle, including the regulation of cyclin-dependent kinases (CDKs) by cyclins and CDK inhibitors, as well as the role of phosphorylation events. The complexity of cell cycle regulation is reflected in the various alterations leading to uncontrolled cell proliferation and cancer development. Targeting the cell cycle, particularly CDKs, presents unique opportunities for drug discovery. The review discusses different families of CDK inhibitors that act through ATP competition, with at least three compounds (flavopiridol, UCN-01, roscovitine) currently in clinical trials. The regulation of the cell cycle involves multiple checkpoints, such as the G1/S and G2/M checkpoints, which ensure the integrity of DNA and the proper alignment of chromosomes during mitosis. Mutations in genes encoding CDKs, cyclins, CDK-activating enzymes, CDK inhibitors, and checkpoint proteins are common in cancer, leading to deregulation of the cell cycle. The review also highlights the development of CDK inhibitors as potential anticancer drugs, including purine analogues, plant cytokinin analogues, pyrimidine analogues, butyrolactones, flavonoids, paullones, indolinones, and other non-specific CDK inhibitors. These inhibitors have shown promise in preclinical studies and clinical trials, offering new therapeutic options for cancer treatment.