Patients with high-grade spondylolisthesis may present with back and/or leg pain and associated disability. Surgery should be considered for intractable pain, functional limitation, documented progression, or neurological deficit. Surgical care may involve posterior instrumented fusion with interbody fusion from the anterior or transforaminal/posterior approach. Interbody fusion allows for the mobilization of the disc for reduction and increases the chance of solid arthrodesis. Preoperative assessment of anatomy, goals of correction, and surgeon expertise and preference may determine the most appropriate operative approach. Successful restoration of the slip angle and achieving solid arthrodesis are factors that most closely predict long-term improvement in health-related quality of life.