During the past decade, 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) has rapidly evolved from a pure research modality to a clinical necessity. FDG-PET was introduced to determine the state of brain function in physiologic and pathologic states. Its use as a powerful tool to diagnose, stage, and monitor patients with a variety of malignancies has been truly revolutionary. However, FDG is a nonspecific tracer and it has been found to accumulate at sites of infection and inflammation. It is becoming evident that PET imaging will play a major role in the treatement of patients with suspected infection and inflammation. PET has been shown to be particularly valuable in the evaluation of chronic osteomyelitis, infected prostheses, sarcoidosis, fever of unknown origin, and acquired immunodeficiency syndrome. Because of its ability to quantitate the rate of FDG uptake, PET may prove to be a powerful modality for the monitoring of disease activity and response to therapy. Novel PET tracers are being tested for imaging infection and inflammation that may further enhance the role of this technique in the appropriate clinical setting. PET imaging to detect and characterize infection and inflammation may become a major clinical indication in the day-to-day practice of medicine.