The recent development of hybrid molecular imaging equipment for both conventional nuclear medicine (e.g., SPECT/CT) and PET (e.g., PET/CT) has raised evidence of the impact of SPECT and PET performed with suitable infection imaging agents and co-registered with CT in the diagnosis of IE. Their unique whole-body exploring ability, i.e., to detect multiple sites of disease with a single examination, has been proven effective in guiding clinical management of patients in view of the selection of optimal treatment strategy. Radiolabeled leukocytes scintigraphy and [18F]FDG-PET/CT have been recently included in the 2015 Guideline for the management of infective endocarditis and proposed as diagnostic tools in the diagnostic flow chart of IE. In...