In intensity-modulated radiation therapy (IMRT), precise target delineation is important to avoid underdosing areas at risk for recurrence and overdosing adjacent normal tissue. In postoperative radiation therapy of patients with head and neck cancer (HNC), surgical extirpation of tumor, anatomic changes resulting from tissue removal, and surgical reconstruction often obscure anatomic detail and may make it difficult to identify high-risk target volumes at postoperative planning computed tomography (CT). Positron emission tomography (PET)/CT can significantly affect CT-based tumor contours by providing information on both biologic and metabolic features of cancer. To incorporate diagnostic PET/CT into target delineation at postoperative CT, an advanced image registration method is required to overcome significant differences in patient position and anatomy between the imaging studies. Rigid registration can account for only linear or uniform transformation between the imaging datasets within six degrees of freedom (three rotations and three translations). However, deformable registration can account for significant temporal and anatomic changes between the corresponding images by computing nonlinear and nonuniform relationships between the volume elements across the imaging datasets. Use of deformable registration to integrate preoperative PET/CT with postoperative treatment planning CT is a powerful tool for target volume delineation in HNC patients undergoing postoperative IMRT.