Recent discoveries in diverse fields of biomedical research have merged to reveal the molecular basis of cell cycle control and a critical role of subverting this homeostatic mechanism in cancer development. At the heart of these processes lies a late G1 checkpoint governed by the "RB pathway" whose molecular composition, functions, and cancer-associated defects are briefly evaluated in this review. This exciting new knowledge raises a plethora of conceptual issues in cell biology, with potential practical implications for biotechnology and medicine.