Avascular necrosis (AVN) of the hip is one of the unsolved problems in orthopedics, especially with regard to drug therapy. Only a few studies exist using a long-term approach with vasodilating agents such as prostaglandins, anticoagulants, hormones, as well as lipid lowering and bone protective drugs such as bisphosphonates. However, using these medications several studies have demonstrated a significant reduction in pain, in the destruction of the femoral head as well as in overall disability. This resulted in a reduced need for joint replacement in patients with AVN and to a substantial improvement in quality of life. Of note, drug therapy should be initiated in the early phases of AVN as later stages appear to be less responsive to medication.