Systemic chemotherapy plays a central role in the management of bladder cancer. Common combinations for muscle invasive and metastatic disease include gemcitabine and cisplatin, or dose-dense methotrexate, vinblastine, doxorubicin and cisplatin. Cisplatin works by causing DNA cross-linking, and gemcitabine inhibits DNA synthesis by “masked termination”. Common toxicity profiles of chemotherapy regimens include myelosuppression, nephrotoxicity and neuropathy. Chemotherapy agents are also used as radiosensitisers such as mitomycin and 5-fluorouracil or carbogen and nicotinamide. Both make radiotherapy more effective and improve locoregional control.