Chemotherapy plays a pivotal role in the treatment of numerous urological malignancies. This chapter examines the expanding role of chemotherapy in the treatment of urological cancers, including bladder, prostate, testicular, renal cell, and penile malignancies. We discuss the primary mechanisms of chemotherapy and outline the main types of chemotherapeutic agents used in these cancers. Key chemotherapy regimens are reviewed, focusing on their applications in neoadjuvant, adjuvant, and metastatic settings. The chapter also explores essential pharmacokinetic considerations, including dose intensity, common side effects and addresses chemotherapy resistance.