Haematopoietic cell number is maintained by a delicate balance between cell proliferation, differentiation and death. Gene knockout studies in mice have revealed the complex roles of cyclins, CDKs, and CDK inhibitors in regulating cell proliferation and differentiation in the haematopoietic system. These studies point to families of cell cycle regulators which display both redundant and unique roles within a lineage and developmental-stage specific manner. Moreover, the promiscuity of these cell cycle regulators is critical for haematopoietic cell proliferation and differentiation. In this review, we discuss the current evidence from mouse models that the complexity and multifarious nature of the haematopoietic system is critical for its form and function.