This review summarizes the results of first-line and second-line systemic chemotherapy for advanced urothelial carcinoma as well as data from adjuvant and neoadjuvant trials for locally advanced bladder cancer. Whereas conventional systemic chemotherapy prevailed for over two decades, targeted therapeutics have been introduced to treat urothelial cancer during recent years. As in other tumor entities, molecular profiling will presumably emerge in the future as a means to tailor individual therapy.