Venous thromboembolism accounts for approximately 600,000 hospitalizations and 50,000 deaths per year in the United States. Many inherited blood disorders predispose patients to this disorder. The most common of these disorders is factor V Leiden. Factor V Leiden thrombophilia is an inherited disorder, mutation, of the mechanisms of blood clotting. The mutation causes resistance to activated protein C and thus causes a defect in the natural anticoagulation system. This predisposes patients to recurrent deep vein thrombosis and in combination with other risk factors can cause significant morbidity. This article discusses the pathophysiology, disease characteristics, risk factors for venous thromboembolism, diagnosis and testing, management of factor V Leiden, and implications for nursing in regard to factor V Leiden. The frequency of factor V Leiden and its prevalence in thromboembolic disease emphasize the need for nursing professionals from many diverse backgrounds to better understand the consequences of the factor V Leiden mutation.