Renal cell carcinoma is the most common neoplasm of the kidney. It is a heterogeneous disease, comprised of different histological variants with a distinct clinical course, genetics and response to treatment. The various subtypes identified include clear cell, papillary and chromophobe, among others. Chromophobe renal cell carcinoma is a rare variant and accounts for 5% of all cases. These tumors are macroscopically larger when compared with other forms and are commonly diagnosed at an early stage. Despite significant advances in renal cell carcinoma therapeutics in the past decade, no standard treatment has been identified for advanced chromophobe renal cell carcinoma. Nevertheless, new molecular insights have recently become available. A familial form of renal cell carcinoma, the Birt–Hogg–Dubé syndrome, has been described and the knowledge obtained has opened research opportunities in the therapeutic arena of chromophobe renal cell carcinoma. The following manuscript will endeavor to provide an overview of this uncommon entity including pathology, epidemiology, genetics, clinical aspects, and current and future treatment options.