Genetic instability is considered to be a major driving force of malignancy of cancer cells, and at least some of cancer-associated genetic instability is known to be caused by defects in the cell cycle checkpoint control. Patients of the cancer-prone genetic disorder ataxia telangiectagia frequently develop malignant lymphoma and their cells are defective in γ-irradiation responsive checkpoint control, whereas cells inactivated for the p53 recessive oncoprotein are defective in DNA damageinduced checkpoint control and develop genetic instability. Cells contain two major cell cycle checkpoint control systems: DNA-replication checkpoint, DNA-damage checkpoint. These checkpoint systems are thought to consist of three functionally distinct components: sensors, checkpoint signal transducers and cell cycle effectors. Recent rapid progress in the identification of these components is beginning to prove this conceptual model and the generality of the checkpoint system among eukaryotes. The full understanding of the cell cycle checkpoint control system will provide deeper insights into the highly complex mechanisms of carcinogenesis and highlight possible targets for cancer therapy.