Infective endocarditis develops when aggravating conditions damage the endothelial lining of the heart and create a nidus of infection. The nidus triggers a cytokine-mediated inflammatory response, which can lead to platelet aggregation and thrombus formation. Bacteria or fungi in the blood can then adhere to the thrombus and colonize, proliferate, and form vegetations. Staphylococcus aureus, Streptococcus species, and Enterococcus species comprise more than 80% of identified bacterial pathogens in cases of infective endocarditis. Endocarditis should be considered in any patient with fever or sepsis of unknown origin. Fever is the most common presenting feature in acute endocarditis, although it is uncommon in subacute cases. New or worsening heart murmur is a typical feature. Initial evaluation includes obtaining blood cultures and echocardiography. Use of the 2023 Duke Criteria is recommended to confirm diagnosis. Empiric intravenous antimicrobial therapy, infectious source control, and expert consultation from a multi-disciplinary team are the mainstays of initial treatment. Patients should also be monitored for surgical indications and development of complications. Patients with a history of endocarditis may benefit from antibiotic prophylaxis before certain procedures and should be counseled on the importance of maintaining oral and skin hygiene to reduce risk.