According to current guidelines, patients with muscle-invasive urothelial carcinoma (pT2-pt4a pN0) should be offered neoadjuvant cisplatin-containing chemotherapy before radical cystectomy. If not used neoadjuvantly, chemotherapy can be administered in the adjuvant setting (for > pT3 or pN+ disease). Both neoadjuvant and adjuvant therapy lead to improved overall survival. In the adjuvant setting, the checkpoint inhibitor nivolumab has also been approved for treatment of PD-L1-positive tumors (tumor proportion score [TPS] ≥ 1%). On the one hand, real-world evidence shows that cisplatin-fit patients often do not receive chemotherapy and, on the other hand, that a relevant proportion of patients are also not suitable for cisplatin-based chemotherapy. Further multimodal therapeutic strategies are hence urgently needed to improve the prognosis of affected patients. In particular, the use of antibody-drug conjugates and combination strategies involving checkpoint inhibitors are currently being intensively researched.