Infective endocarditis (IE) is an inflammatory process that occurs in the endocardium and also in implantable cardiac devices, the septum between the heart chambers, and in particular the heart valves, whether biological or prosthetic, this process comes from infection by some microorganism, especially bacteria. In 2023, the International Society of Cardiovascular Infectious Diseases (ISCVID) reformulated the diagnostic criteria, in particular those related to microbiological aspects. The aim of this study is to discuss the modified Duke criteria, therapeutic measures, and future challenges. The present study is a narrative bibliographical review that analyzed scientific production in online databases. Because it is a rare pathology, its annual incidence is between 3 and 10 cases per 100,000 people, and it is twice as common in males. Its treatment is complex, but its mainstay is antibiotic therapy and, when necessary, cardiac surgery. Empirical antibiotic treatment should be carried out as soon as possible after blood culture tests have been taken. In conclusion, IE is one of the most laborious and difficult medical conditions for physicians to practice, so it is important to employ a systemic approach based on scientific evidence for diagnostic investigation and therapeutic care for good results and patient well-being.