The article discusses the role of cyclins and cyclin-dependent kinases (Cdks) in the mammalian cell cycle, particularly in the G1 phase. Traditionally, it was believed that D-type and E-type cyclins, along with their associated Cdks, are essential for cell cycle progression. However, recent studies in mice have shown that these genes are not strictly essential for fetal development. The authors review the previous understanding of G1 regulation, including the functions of cyclins and Cdks in yeast, flies, and frogs, and their roles in mammalian cells. They highlight that while cyclin D-Cdk4 complexes are crucial for cell division, they can be partially compensated by other mechanisms, such as the activation of cyclin E-Cdk2. The article also discusses the phenotypes of mice lacking specific cyclin or Cdk genes, which revealed that some cell cycle functions can be rescued by other regulatory pathways. The findings suggest that the prevailing dogma about the essential role of cyclins and Cdks in the cell cycle may need reevaluation, and that the cell cycle machinery has more redundancy and compensatory mechanisms than previously thought. The implications of these findings for cancer biology are also discussed, particularly the resistance of cells lacking cyclin D or Cdk4 to oncogene-induced transformation.The article discusses the role of cyclins and cyclin-dependent kinases (Cdks) in the mammalian cell cycle, particularly in the G1 phase. Traditionally, it was believed that D-type and E-type cyclins, along with their associated Cdks, are essential for cell cycle progression. However, recent studies in mice have shown that these genes are not strictly essential for fetal development. The authors review the previous understanding of G1 regulation, including the functions of cyclins and Cdks in yeast, flies, and frogs, and their roles in mammalian cells. They highlight that while cyclin D-Cdk4 complexes are crucial for cell division, they can be partially compensated by other mechanisms, such as the activation of cyclin E-Cdk2. The article also discusses the phenotypes of mice lacking specific cyclin or Cdk genes, which revealed that some cell cycle functions can be rescued by other regulatory pathways. The findings suggest that the prevailing dogma about the essential role of cyclins and Cdks in the cell cycle may need reevaluation, and that the cell cycle machinery has more redundancy and compensatory mechanisms than previously thought. The implications of these findings for cancer biology are also discussed, particularly the resistance of cells lacking cyclin D or Cdk4 to oncogene-induced transformation.