Biomarkers and novel therapies for bladder cancer are rapidly developing. Here, Thomas Powles, MBBS, MRCP, MD, of Barts Cancer Institute, London, UK, summarizes the potential and current status of immunotherapies and chemotherapies in the second-line treatment of metastatic urothelial cancer, questioning whether emerging therapies can be shifted to the first-line setting. Prof. Powles speaks from the European Society for Medical Oncology (ESMO) 2018 Congress, in Munich, Germany, further highlighting a potential role for PARP and FGF inhibitors in changing the current landscape of urothelial carcinoma treatment, as well as discussing second-generation biomarkers.