von Willebrand disease (VWD), the most common inherited bleeding disorder, is caused by quantitative or qualitative deficiencies in the von Willebrand factor (VWF) protein. VWF is crucial for platelet adhesion and aggregation at sites of vessel injury and also for stabilizing and transporting factor VIII (FVIII) to these sites. Clinical manifestations of VWD vary from mild to severe bleeding including mucosal and soft tissue bleeding, bleeding with surgery or trauma, muscle and joint bleeding, and female-specific bleeding such as heavy menstrual and other gynecological, pregnancy, and postpartum bleeding. Diagnosis of VWD includes a personal and family history of bleeding and abnormal laboratory assays for VWF. Treatment for VWD includes VWF replacement and adjunctive therapies including antifibrinolytics and hormonal therapy for gynecologic bleeding. This chapter will review VWD with emphasis on clinical features, diagnosis, and management pertaining to adolescent females.