The use of positron-emission tomography in clinical practice is increasing, particularly with the use of 18-fluoro-2-deoxyglucose (FDG) for oncological studies. As in other imaging modalities, it is important to be aware of normal variants and benign diseases that may mimic more serious pathology. Uptake of FDG in a number of sites may be variable. Uptake of FDG may be seen normally in the skeletal muscle after exercise or under tension, in the myocardium, in parts of the gastrointestinal tract, especially the stomach and cecum, and in the urinary tract. Some causes of increased physiological uptake are avoidable, and measures can be taken to minimize accumulation, thus aiding study interpretation. Inflammatory lesions may cause an increase in FDG uptake, but not usually to the same degree as malignancy. Benign disease such as Paget's disease of bone, sarcoidosis, and tuberculosis may cause uptake that occasionally mimics that of malignancy. Typical examples of a number of physiological and benign variants are described and illustrated.