- INTRODUCTION: Urothelial carcinoma is one of the most common cancers in the western world and, until recently, had limited therapeutic options. The contemporary advancement of immune checkpoint inhibitors (ICI) has heralded a new era for these patients and represents a major shift in the evolving treatment landscape. AREAS COVERED: This article provides a comprehensive summary of the currently available treatments for metastatic urothelial carcinoma (mUC). The authors also review ongoing, phase-III studies with novel therapeutic targets and highlight recent insights into tumor biology that may help better understand the disease. EXPERT OPINION: The treatment landscape for first-line therapy of mUC continues to include platinum-based chemotherapy for patients who are eligible. While the approval of ICI has changed the management in those who are post-platinum or platinum-ineligible, the wider use of ICI in the first-line setting requires further clarity given recent FDA announcements. Maintaining the remarkable progress in mUC may depend upon ongoing phase-III studies evaluating treatment options beyond ICI. Better prognostication and identification of those unlikely to respond to ICI remain important unanswered questions, particularly as this class of agents moves further along the disease spectrum of non-metastatic UC.