Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) has been effective for the diagnosis, staging, and restaging of malignancies of the head and neck region. However, lack of anatomic landmarks, variable physiologic uptake, and asymmetric FDG distribution in several altered physiologic states can confound image interpretation. In addition, many benign causes and several artifacts can simulate physiologic or pathologic FDG uptake in the head and neck. Combined PET-computed tomography (CT) is a unique imaging modality that permits anatomic and functional imaging on a single scanner with nearly perfect coregistration. Combined PET-CT provides information that cannot be obtained with PET or CT alone. In particular, PET-CT facilitates the interpretation of FDG uptake in the head and neck, an area that is characterized by dense and complex anatomic structures. An atlas of FDG uptake in this anatomic region was compiled on the basis of combined PET-CT findings in 11,000 patients. In general, patterns of FDG uptake were variable and often reflected patient activity during or immediately preceding the uptake phase. With the growing interest in PET-CT, interpreting radiologists and nuclear medicine physicians must be familiar with the patterns of FDG uptake in the head and neck to avoid misinterpretation or mis-diagnosis.