The role of nuclear imaging in the characterization of high-risk atherosclerotic plaque is increasing thanks to its high sensitivity to detect radiopharmaceuticals signal in tissues. Currently, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most studied and widely used radiopharmaceutical for the molecular imaging of atherosclerotic plaques with positron emission tomography (PET). [18F]FDG PET is a valuable tool to non-invasively detect, monitor and quantify inflammatory processes occurring in atherosclerotic plaques. The aim of this review is to gather insights provided by [18F]FDG PET to better understand the role of inflammation in the definitions of the vulnerable plaque and the vulnerable patient. Alternatives radiopharmaceuticals targeting inflammation and other potential high-risk plaque related processed are also discussed.