Cardiac Implantable Electronic Device (CIED) infections are an emerging clinical issue. There are no national recommendations on the management of these infections, also due to the limited number of dedicated and high quality clinical studies. Therefore, researchers from southern Italian centres have decided to share the clinical experience gathered so far in this field and report practical recommendations for the diagnosis and treatment of adult patients with CIED infection or endocarditis. Here we review the risk factors, diagnostic issues (microbiological and echocardiographic) and aetiology, and describe extensively the best therapeutic approach. We also address the management of complications, follow-up after discharge and the prevention of CIED infections. In this regard, a multidisciplinary approach is fundamental to appropriately manage the initial diagnostic process and the comorbidities, to plan proper antimicrobial treatment and complete percutaneous hardware removal, with the key support of microbiology and echocardiography.