A major challenge for molecular diagnosis of bladder cancer is the subdivision of tumors beyond histological classifications into clinical relevant molecular subgroups. The evolution of molecular high-throughput techniques assessing a large number of molecular features at the same time has made comprehensive investigation of these subgroups possible. Molecular signatures for disease stage, grade, progression, carcinoma in situ, presence of metastases, and treatment response have been reported. Some of these molecular signatures are now being tested in multicenter studies with the purpose of introducing these into the clinic, for planning of follow-up and treatment selection. In this review, we define the clinical relevant subgroups and give an overview of recent advances in marker identification in the field of non-muscle invasive and invasive bladder cancer. Furthermore, we stress the methods and materials needed to translate such molecular profiles into clinically useful tests.