Activation of bladder cancer stem cells (CSCs) can drive progressive resistance to chemotherapy. Cytotoxic therapy is initially effective in debulking tumours, but it has now been shown that apoptosis promotes release of prostaglandin E2 (PGE2), which stimulates quiescent CSCs to divide, proliferate and repopulate the tumour. Inhibition of PGE2 signalling blocks CSC repopulation, and attenuates progressive chemoresistance in xenograft tumours, and might represent a new treatment paradigm for patients with bladder cancer.