Infective endocarditis (IE) is defined by infection of either a native or prosthetic heart valve, endocardial surface or any cardiac prosthetic device. It is a disease of both the developed and developing world, although IE has evolved in the developed world to a disease markedly different to the disease encountered in the developing world. IE in developed nations is mainly a disease of older patients with degenerative heart valve disease or cardiac prosthetic material, with virulent Staphylococci the most common causative organism. Data regarding the epidemiology of IE in South Africa, a developing country, is limited. The available data suggest it is still a disease of younger patients with rheumatic heart disease (RHD), associated with penicillin-sensitive Streptococcal infection. Although novel diagnostic techniques and improved therapeutic options has emerged, the 1-year mortality rate has remained high in both the developed and developing world at around 30%. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.