Infective endocarditis (IE) is an uncommon but life-threatening condition characterized by infection and inflammation of the endocardial surface of the heart, most commonly affecting native or prosthetic valves. Recent data indicate in-hospital mortality rates ranging from 15% to 25%, with evidence of increasing mortality even in high-income countries. Beyond its fatal potential, IE poses a major public health burden, accounting for over 1.7 million disability-adjusted life years (DALYs) globally in 2019. This review aims to discuss recent advancements in the diagnosis and management of IE given the shifting epidemiology and pathogen profile of the disease. There is a rising incidence of healthcare-associated IE and an expanding population of vulnerable patients, including the elderly and those with prosthetic material or indwelling catheters. Diagnostic capabilities have rapidly advanced with the adoption of modalities such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiac CT, and cardiac magnetic resonance (CMR), particularly in patients with prosthetic valve endocarditis or culture-negative presentations. Additionally, the expanding indications for surgical intervention and increasing antimicrobial resistance have added complexity to management decisions. These developments underscore the need for a comprehensive review to support healthcare providers in navigating the modern diagnostic and therapeutic landscape of IE.