Over the last 20 years, primary FSGS has emerged as one of the leading causes of idiopathic nephrotic syndrome in adults, particularly among African Americans. In nephrotic patients, progression to ESRD often occurs over the course of 5–10 years, whereas non-nephrotic patients and those entering a remission have an extremely favorable prognosis. As a result, it is in patients who remain persistently nephrotic despite conservative therapy that a more aggressive therapeutic approach is taken. Primary FSGS was once considered an entity nonresponsive to prednisone or immunosuppressive agents, but it has become apparent over the last 20 years that a substantial portion of nephrotic adults with primary FSGS do respond to treatment with a significantly improved prognosis. The recent histologic classification proposed for FSGS has provided additional insights into the prognosis and response to therapy. This article reviews the current knowledge regarding the presentation, prognosis, and therapeutic approach in adults with primary FSGS.