The diagnosis of infective endocarditis (IE) is challenging and requires the association of morphological features suggestive of valvular infection such as the presence of vegetations or abscesses identified usually with echocardiography and positive blood culture or serologies suggestive of systemic bacterial infection. In the past 5 years, several groups confirmed the incremental value of FDG-PET imaging and radiolabeled leukocyte scintigraphy over echocardiography for the diagnosis of IE. Based on the latter studies, the presence of abnormal activity in the perivalvular region on either FDG-PET imaging or radiolabeled leukocyte scintigraphy has been added as a major criterion for the diagnosis of IE in the guidelines recently published. Nuclear physicians should therefore learn not only the imaging criteria in favor of active IE but also the pitfalls of these nuclear imaging techniques in order to give a useful answer to the referring physician for the management of these patients. In fact, the diagnosis of IE is often complex and requires the integration of multiple clinical, biological, and imaging parameters. Multi-disciplinary teams including cardiologists, infectious disease physicians, cardiac surgeons, and radiologists have been therefore set up in several institutions to discuss the diagnosis and management of patients with a suspicion of IE. It is now time for nuclear cardiologists to join the team.