It has been reported that fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) may detect the inflammatory state and macrophage burden of atherosclerotic plaques and potentially identify vulnerable plaques. However, published reports have been inconsistent in this area. Tavakoli et al ( 1 ) hypothesized that differential regulation of macrophage glucose metabolism by macrophage colony-stimulating factor (M-CSF; inflammation resolving) and granulocyte-M-CSF (GM-CSF; proinflammatory) may contribute to the inconsistency of FDG vessel wall inflammation. After the induction of inflammatory and metabolic profiles, both M-CSF and GM-CSF generated comparable levels of glucose uptake in cultured macrophages and murine atherosclerotic plaques. These findings suggest that although FDG uptake is an indicator of vascular macrophage burden (total number of macrophages), it may not necessarily differentiate morphologically unstable (inflammatory) from stable (noninflammatory) atherosclerotic plaque. Moreover, although atherosclerosis is characterized by macrophage-predominated inflammation, there is a wide range of other vascular diseases in which macrophages and inflammation play an important role in the absence of atherosclerosis. FDG uptake will be indistinguishable in atherosclerosis from large-artery inflammatory vascular disease, such as Takayasu arteritis, chemotherapy- or radiation-induced vascular inflammation, or foreign-body reaction, such as synthetic arterial graft. Because of the nonspecific nature of FDG uptake by any cell (upregulated under hypoxic conditions or other microenvironmental factors), this work calls for a more cautious approach to interpreting vascular FDG uptake as indicative of inflammatory atherosclerosis in the clinical setting.