The symptoms and complications of von Willebrand disease (VWD) correlate with subtype classification and degree of qualitative or quantitative deficit. It is more commonly diagnosed in females than males due to the hemostatic challenges of menstruation and childbirth. In childhood, bruising, prolonged bleeding from cuts, and epistaxis are common presenting symptoms in both males and females. VWD patients are also at increased risk of postoperative hemorrhage, and a higher likelihood of requiring surgical re-exploration and red cell transfusion if precautions are not taken. The management of VWD varies depending on the subtype, disease severity, specific complication, and clinical setting. The general principles of VWD management are focused on preventing symptomatic bleeding, improving quality of life, treating acute bleeding episodes, and ensuring hemostasis with procedures and childbirth. Therapeutic agents available to the clinician managing VWD include desmopressin, von Willebrand factor concentrates, antifibrinolytic agents, and hormonal agents depending on the clinical scenario and disease type. Recent management guidelines highlight obstetrical and gynecological care, perioperative management, approach to cardiovascular-related events, and expanding use of prophylaxis in type 2 and 3 VWD. In this chapter, we discuss the management of VWD in various clinical settings, including minor procedures, major surgery, heavy menstrual bleeding (HMB), obstetric care, cardiovascular intervention, and long-term prophylaxis.