RB1, the gene that encodes the retinoblastoma tumour suppressor protein (RB), is mutated in one-third of human cancers. Although widely appreciated as a transcriptional coregulator, Jacqueline Lees and colleagues have found that RB also functions outside of the nucleus at the mitochondrial membrane. Recombinant RB was able to bind BAX in its active conformation and trigger the permeabilization of mitochondria and liposomes in vitro, and to interact directly with BAX in vivo. Moreover, a mutant form of RB that was targeted only to the mitochondria promoted apoptosis induced by tumour necrosis factor and other apoptotic stimuli, and was able to block further tumour development when expressed in Rb1−/−Trp53−/− tumours in mice.