D-type cyclins (cyclin D1, D2 and D3) and their associated cyclin-dependent kinases CDK4 and CDK6 were thought to represent important, perhaps essential components of the core cell cycle apparatus. However, recent analyses of mice lacking D-cyclins, or CDK4 and CDK6 reveal that these proteins are critically required for proliferation only in the selected cell types. Intriguingly, several compartments can develop in the absence of cyclin D-CDK4/6 activity, revealing that these cells can proliferate in a cyclin D-independent fashion.