Carcinoma in situ (CIS) of the bladder is defined as a high-grade flat lesion confined to the mucosa. Intravesical treatment with BCG (Bacillus Calmette-Guerin) is commonly used to reduce the risk of its recurrence and progression; however, patients present a heterogeneous clinical behavior, and an important proportion of them primarily do not respond. In this chapter, we evaluate the parameters concerning the diagnosis, treatment strategies, follow-up, prognosis, and oncological outcomes in patients with CIS of the bladder. Evidence shows that new optical imaging modalities significantly increase the detection rate of CIS and that BCG immunotherapy remains the first-line therapy in patients with CIS of the bladder; however, after treatment, adequate follow-up is necessary. Clinicopathological factors remain the main indicators of BCG response, recurrence, and progression. There are no robust data that allow considering other agents as an alternative to BCG immunotherapy.