The incidence of bladder cancer has increased in the past decade, and mortality from bladder cancer remains a substantial public health burden. After 3 decades of minimal progress in the treatment of advanced-stage disease, recent advances in the genomic characterization of urothelial cancer and breakthroughs in bladder cancer therapeutics have rejuvenated the field. This review highlights the landmark clinical trials of chemotherapy in both the neoadjuvant and advanced or metastatic urothelial carcinoma settings. We describe treatment paradigms for multimodal treatment of locally advanced bladder cancer, including discussion on bladder preservation strategies. Lastly, we discuss novel immunomodulatory, targeted, and combination therapies in development for the treatment of advanced urothelial carcinoma.