Infective endocarditis (IE) is a severe infectious disease affecting cardiac valves (either native or prosthetic) or implantable cardiac devices, and it is associated with high rates of morbidity and mortality. Recent data from the Global Burden of Disease study have shown a significant increase in both the incidence and mortality of IE. One-year mortality following diagnosis can reach up to 30%. IE can present with a wide range of clinical manifestations, and its course may be complicated by systemic embolic events or intracardiac complications such as abscess formation or prosthetic valve dehiscence. Echocardiography remains the first-line imaging modality; however, an integrated multimodality imaging approach is increasingly adopted in contemporary practice, incorporating both cardiac computed tomography and positron emission tomography. A multidisciplinary approach involving cardiologists, cardiac surgeons, internists, infectious disease specialists, and nuclear medicine physicians is often required to ensure accurate diagnosis and effective treatment of IE. The prognosis of infective endocarditis depends on early diagnosis, appropriate antimicrobial therapy, and timely surgical intervention when indicated. This review aims to summarize the current knowledge on IE, from pathophysiological insights to surgical strategies. It also focuses on practical recommendations to address the most pressing unmet clinical needs through a multidisciplinary approach.