IE is a fascinating disease that continues to challenge the clinicians. Over the last several decades, there have been marked changes in its presentation. The morbidity and mortality have markedly improved by early diagnosis and prompt treatment using highly effective antibiotic regimens and early valve replacement surgery whenever necessary. Early diagnosis is possible by improvement in blood culture techniques and advances in transthoracic and transesophageal echocardiographic approaches. This article has reviewed the pathogenesis, microbiology, clinical presentation, diagnostic methodology, treatment, and prevention of IE.