This chapter outlines the basic principles of nuclear imaging as applied to imaging of the atherosclerotic plaque. The small size of most atherosclerotic lesions and their anatomical proximity to other structures places exacting demands on nuclear imaging systems. In single photon emission computed tomography (SPECT) and PET the detected photon emission is corrected to account for errors due to attenuation, scatter, random decay events and dead time, following which 2D and 3D topographical images can be reconstructed. Vulnerable lesions are characterized by high levels of low density lipoprotein (LDL) accumulation, oxidation and phagocytosis by plaque macrophages and foam cells. The recognition that fluorine-18 labelled deoxyglucose (FDG)-PET might have a role in imaging inflammation led to its use in diagnosing and following patients with systemic vasculitides. Vulnerable plaques provide a highly thrombogenic substrate and have often gone through both symptomatic and asymptomatic episodes of rupture, thrombosis and repair.