The implantation of biological or mechanical heart valves, pacemakers, defibrillators, and prosthetic vascular grafts can save the life of patients with valvular heart disease, conduction disorders, arrhythmia, or vascular disease. The use of these devices has increased in the general population. Antibiotic prophylaxis is indicated to prevent cardiovascular device-related infections, which are uncommon, but have high associated morbidity and mortality. We review the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of these infections. Staphylococci are the most common etiological agents, and the infection is thought to result from contamination during device implantation or in the early postoperative period. Positive blood culture status, and diagnostic imaging (transesophageal echocardiography, computed tomography, magnetic resonance imaging) and nuclear medicine study (scintigraphy using labeled leukocytes) are the basic tools to establish the diagnosis. Treatment is complex and requires prolonged antibiotic administration targeting the isolated organisms, and device removal to attain cure.