Multiple surgeries are often required to manage segmental bone loss because of the complex mechanics and biology involved in reconstruction. These procedures can lead to prolonged recovery times, poor patient outcomes, and even delayed amputation. A two-stage technique uses induced biologic membranes with delayed placement of bone graft to manage this clinical challenge. In the first stage, a polymethyl methacrylate spacer is placed in the defect to produce a bioactive membrane, which appears to mature biochemically and physically 4 to 8 weeks after spacer placement. In the second, cancellous autograft is placed within this membrane and, via elution of several growth factors, the membrane appears to prevent graft resorption and promote revascularization and consolidation of new bone. Excellent clinical results have been reported, with successful reconstruction of segmental bone defects >20 cm.