Chemoprevention of cancer can be accomplished using primary, secondary, or tertiary strategies. Tertiary chemoprevention has been the predominant approach for bladder cancer and addresses the need for preventing the occurrence of second primary cancers in patients who have previously been treated for cancer. Because non-muscle-invasive bladder cancer is associated with a high risk of recurrence, tertiary chemoprevention has been studied in this population. Although considerable preclinical data has demonstrated the feasibility of this approach, application to the clinical setting has met with limited success. This review discusses chemoprevention of bladder cancer and focuses on the drugs used in chemoprevention investigations and clinical study design.