Apoptosis is essential for the removal of unwanted or damaged cells from an organism. A decrease in the susceptibility of cells to apoptosis can not only cause cancer, but can also result in resistance to anti-cancer drugs that act by inducing apoptosis. BCL2 is an anti-apoptotic protein that prevents disruption of the mitochondrial membrane potential and the release of cytochrome c. It is overexpressed in a variety of tumours, where it confers resistance to conventional chemotherapy. On page 1568, Richa Singh and Neeru Saini now describe the pro-apoptotic effects of three microRNAs (miRNAs) that downregulate BCL2 expression. Using computational and experimental approaches, they show that miR-24, miR-195 and miR-365 negatively regulate BCL2 by binding to the 3′ UTR of the BCL2 gene. Overexpression of each of the miRNAs reduces BCL2 expression and BCL2 protein levels and, furthermore, leads to apoptosis through disruption of the mitochondrial membrane potential and the release of cytochrome c. Finally, the authors report that overexpression of these miRNAs in MCF7 breast cancer cells augments the apoptotic effect of the etoposide, by increasing the proportion of cells that undergoes apoptosis after exposure to the chemotherapeutic agent. They hope that this miRNA-mediated pro-apoptotic effect can be exploited to develop new therapeutic strategies.