Infective endocarditis (IE) is a systemic septic disease that is a microbial infection of the endothelial surface of the heart. Despite advances in medical, surgical, and critical care interventions, IE remains a life-threatening illness. Therefore, it is important to promptly diagnose it using the modified Duke criteria. These criteria integrate factors predisposing patients to the development of IE, the blood-culture isolates and persistence of bacteremia, and echocardiographic findings, along with other clinical and laboratory information. Positive blood culture and a positive echocardiogram are the cornerstones of IE diagnosis. Identification of the infecting organisms is of primary importance because this knowledge guides antibiotic therapy. For the detection of vegetation, transesophageal echocardiography has a sensitivity of 76-100%, whereas that of transthoracic echocardiography ranges from 50 to 60%. Transesophageal echocardiography is particularly useful in patients with prosthetic valves and sparse vegetation. Recent studies reported that causative microorganisms of IE are changing. Staphylococcus aureus is now the most common cause of IE in Western countries. This shift is due in part to a higher rate of Staphylococcus aureus infection in patients with cardiac devices (for example, prosthetic valve, pacemaker, and implantable cardioverter defibrillator [ICD]).