Management of patients with hereditary kidney cancer presents a unique challenge for the urologic surgeon, as patients are often at risk for multiple, bilateral renal surgeries. An understanding of the genetic basis of kidney cancer has led to distinct treatment paradigms in both the surgical management of localized disease and the treatment of advanced disease with systemic therapy. Minimizing the number of interventions and subsequent renal compromise, while maximizing oncologic efficacy, is critical in treating these patients. This chapter reviews the genetics of hereditary kidney cancer with a special emphasis on the translation of genetic insights into contemporary management approaches.