Idiopathic retroperitoneal fibrosis (IRPF) is an increasingly recognized syndrome. The development of inflammation and fibrosis in the retroperitoneum most often results in a periaortic mass on computed tomography or magnetic resonance imaging that causes pain and constitutional symptoms. Its organ involvement results in urinary tract obstruction, bowel dysfunction, and venous compression with leg swelling, or thrombosis. The syndrome appears autoimmune in nature, but has no specific immunologic markers. However, nonspecific inflammatory indicators, such as sedimentation rate and C-reactive protein level, reflect disease activity and therapeutic response. Retroperitoneal fibrosis also can arise secondary to inflammatory, infectious, or malignant disease in retroperitoneal organs, in which case treatment is directed at the primary process. However, in patients with IRPF, initial treatment of the local mechanical complications must be followed by medical therapy with corticosteroids or, more recently, the addition of steroid-sparing agents. Although there are no controlled therapeutic trials, a number of reports with as few as 3 or as many as 28 cases describe sustained and effective steroid-sparing treatment with cyclophosphamide, azathioprine or colchicine, or such newer agents as mycophenolate mofetil or tamoxifen. Overall, IRPF responds to corticosteroid therapy initially but recurs without prolonged treatment. Sustained remission can be attained with steroid-sparing treatment. Kidney function can be preserved, and local organ dysfunction can remit for periods of 10 years or more. Although not randomized or controlled, the evidence convincingly supports a combination of initial surgical or urological intervention, along with early corticosteroid therapy for up to 6 months followed by either mycophenolate or tamoxifen for 1 to 3 years. What was previously believed to be an uncommon and challenging syndrome can be treated successfully when recognized by its characteristic presentation.