Entry into, progression through, and exit from the G1 phase of the mammalian cell cycle in response to extracellular mitogenic cues are presumed to be governed by cyclin-dependent kinases (Cdks) regulated by the D-type and E-type cyclins. Studies performed over more than a decade have supported the view that these holoenzymes are important, if not required, for these processes. However, recent experiments in which the genes encoding all three D-type cyclins, the two E-type cyclins, cyclin D-dependent Cdk4 and Cdk6, or cyclin E-dependent Cdk2 have been disrupted in the mouse germ line have revealed that much of fetal development occurs normally in their absence. Thus, none of these genes is strictly essential for cell cycle progression. To what extent is the prevailing dogma incorrect, and how can the recent findings be reconciled with past work?