A number of novel therapeutics are being developed for non-muscle-invasive bladder cancer (NMIBC). Several of these agents have made their way into clinical trials. NMIBC includes a heterogeneous group of tumors with a wide range of recurrence and progression rates that must be considered in the design of clinical trials for these newer agents. Indeed, the goals of novel therapeutics for NMIBC differ depending on the recurrence and progression risk. The authors discuss the clinical experience with novel therapeutics, including alternative chemotherapeutics (apaziquone, docetaxel and gemcitabine), new paradigms for the delivery of chemotherapy, gene therapy and photodynamic therapy, emphasizing the need for appropriate risk stratification and comparison groups for future trials.