Dihydroxyphenylalanine (DOPA) is a neutral amino acid that resembles natural L-dopa (dopamine precursor). It enters the catecholamine metabolic pathway of endogenous L-DOPA in the brain and peripheral tissues. It is amenable to labeling with fluorine-18(F) for PET imaging and was originally used in patients with Parkinson's disease to assess the integrity of the striatal dopaminergic system. The recent introduction and use of hybrid PET/CT scanners has contributed significantly to the management of a series of other pathologies including neuroendocrine tumors, brain tumors, and pancreatic cell hyperplasia. These pathologic entities present an increased activity of L-DOPA decarboxylase and therefore demonstrate high uptake of F-DOPA. Despite these potentially promising applications in several clinical fields, the role of F-DOPA has not been elucidated completely yet because of associated difficulties in synthesis and availability. Unfortunately, the available literature does not provide recommendations for procedures or administered activity, acquisition timing, and premedication with carbidopa. The aim of this paper is to outline the physiological biodistribution and normal variants, including possible pitfalls that may lead to misinterpretations of the scans in various clinical settings.