The retinoblastoma gene family is composed of three members: the retinoblastoma gene, one of the most well studied tumor suppressor genes and two related proteins, p107 and pRb2/p130. These three proteins share many structural and functional features and play a fundamental role in growth control. Intense investigation of these proteins has identified a series of similar cell-cycle regulators and transcription factors with which they interact. Although the precise function of the retinoblastoma gene product and its relatives remains unknown, recent data suggests that they play parallel roles in controlling cell cycle progression and promoting cellular differentiation. In this review, we will attempt to clarify some of the molecular mechanisms by which these three related proteins cooperate to control cellular proliferation and differentiation.