Molecular imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) is increasingly used to diagnose, characterize, and monitor disease activity in the setting of inflammatory disorders of known and unknown etiology. These disorders include sarcoidosis, atherosclerosis, vasculitis, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and degenerative joint disease. Gallium-67 ((67)Ga) citrate, labeled leukocytes with technetium-99m ((99m)Tc) or indium-111 ((111)In), and (18)F-fluorodeoxyglucose (FDG) represent the most widely used radiopharmaceutical agents. However, other preparations, such as labeled murine monoclonal antigranulocyte antibodies and labeled human polyclonal nonspecific immunoglobulin G, chemotactic peptides, interleukins, chemokines, and liposomes, have been used to image inflammation. Also, (99m)Tc nanocolloid scintigraphy has been found to be suitable for bone and joint diseases, especially RA. Among the single photon emitting imaging agents, the recommended radiotracer for abdominal inflammation has been (99m)Tc-hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes. During the last several years, FDG-PET imaging has been shown to have great value for the detection of inflammation and has become the centerpiece of such initiatives. This very powerful technique will play an increasingly important role in the management of patients with inflammatory conditions. FDG-PET can provide valuable information in patients with pulmonary and extrapulmonary sarcoidosis, and is a useful tool for testing the efficacy of various treatments. FDG-PET combined with computed tomography holds great promise for assessing atherosclerosis of the large arteries. This modality is very sensitive in detecting large-vessel vasculitis and can be used to monitor the disease course. FDG-PET is also being used to study the inflamed synovial joints both in the experimental and clinical settings, especially for the investigation and management of RA and degenerative joint disease. This technique also has the potential to become the imaging modality of choice in assessing IBD, replacing radiolabeled autologous leukocyte imaging in this setting. Detection of inflammation in the lungs and airways may improve our knowledge about a multitude of disorders that affect these structures. Therefore, functional imaging, led by FDG-PET imaging, is likely to play an increasingly critical role in assessing inflammatory disorders of known and unknown etiologies, and will improve their management immensely in the future.