Although not cloned in 1971, the RB tumour suppressor gene is famous for being the subject of the Knudson two hit hypothesis. Much has been discovered about RB since then, but how it functions as an tumour suppressor remains enigmatic. Aside from its regulation of the G1 phase of the cell cycle, in particular by suppressing the function of the E2F family of transcription factors, there is increasing evidence that RB regulates other important cellular pathways. Indeed, it is now no longer possible to cover the potential functions of RB and E2F in one bite-size review. Instead, we have commissioned a short series of articles that discuss some of newer strings that have been assigned to the RB bow and some of the questions that still need to be answered.