Acute infective endocarditis is a complex disease with changing epidemiology and a rapidly evolving knowledge base. To consistently achieve optimal outcomes in the management of infective endocarditis, the clinical team must have an understanding of the epidemiology, microbiology, and natural history of infective endocarditis, as well as a grasp of guiding principles of diagnosis and medical and surgical management. The focus of this review is acute infective endocarditis, though many studies of diagnosis and treatment do not differentiate between acute and subacute disease, and indeed many principles of diagnosis and management of infective endocarditis for acute and subacute disease are identical.