Large, full-thickness scalp defects represent a reconstructive challenge that has benefitted greatly from the introduction of microsurgical techniques. The authors review their experience with 16 patients with acquired defects of the scalp for which local or regional reconstructive options were unavailable. The mean age at the time of operation was 44.8 years. Nine patients underwent resection of malignant scalp lesions, followed immediately by free-flap coverage. Six patients required revision procedures for unstable scar as a result of prior trauma (2), old scalp avulsions (2), and multiple intracranial procedures (2). The remaining patient underwent replantation of an acutely avulsed scalp. The free-flap donor sites utilized included latissimus (6), scapular (3), radial forearm (2), rectus abdomnis (2), and omentum (2). Vein grafts were required in four cases. All flaps survived, although one required anastomotic revision and skin grafting for superficial loss. Additional complications were limited to seromas at two latissimus donor sites. Tumor control rates were poor, with all malignancy-associated defects having persistent disease or recurring soon after surgery. All patients eventually achieved full defect coverage. The authors conclude that microsurgical reconstruction is a reliable option for providing stable coverage of large, complex, scalp defects.