Infective endocarditis (IE) is a rare, life-threatening disease with a mortality rate of 25% and significant debilitating morbidities. Although much has been reported on contemporary IE in high-income countries, conclusions on the state of IE in low- and middle-income countries (LMICs) are based on studies conducted before the year 2000. Furthermore, unique challenges in the diagnosis and management of IE persist in LMICs. This article reviews IE studies conducted in LMICs documenting clinical experiences from the year 2000 to 2016. Presented are the causes of IE, management of patients with IE, and prevailing challenges in diagnosis and treatment of IE in LMICs.