Many of the risk factors and pathogenesis of urothelial carcinoma of the renal pelvis are similar to the ones of the more common urothelial bladder cancer. In addition, two endemic nephropathies and two inherited syndromes have been linked with the development of upper urologic cancer. Multiple synchronous or metachronous lesions throughout urinary tract are rather common and should always be sought in the management of this entity. Surgical resection is the treatment of choice in early-stage tumors. The role of adjuvant radiation and chemoradiation for carcinoma of the renal pelvis remains to be redefined, given the advent of conformal approaches and intensity modulation. In non-surgical candidates, chemotherapy remains the mainstay. Metastatic urothelial renal pelvic cancer is usually treated with combination platinum-based chemotherapy. Definitive radiation therapy should be considered in persons with locally advanced/unresectable disease, multiple comorbidities, and/or severely compromised performance status. Recently, the antifolate agent pemetrexed has demonstrated an overall response rate of circa 30% in urothelial carcinoma. New targeted agents, alone or in combination with cytotoxic drugs, are currently being tested in clinical trials and may lead to new and exciting avenues for the therapy of this disease.