The most recent clinical guidelines on the management of infective endocarditis propose findings of multimodality imaging, including nuclear imaging with SPECT/CT or PET/CT, as part of the diagnostic criteria and diagnostic flowchart of infective endocarditis, particularly in patients with suspected prosthetic valve endocarditis. Radiolabelled leukocyte scintigraphy SPECT and 18F-fluorodeoxyglucose PET are sensitive methods to detect sites of infection. Current data indicate that they may contribute to early diagnosis of IE. In this chapter, we will describe the methodology and underlying evidence on the use of nuclear imaging techniques for evaluation of infective endocarditis.