Enterococcus faecalis the more common and virulent species causes serious high-inoculum infections namely infective endocarditis that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. Enterococci is one of the most common causes of hospital-associated infections are responsible for substantial morbidity and mortality. The best cures for these infections are observed with combination antibiotic therapy. Optimal treatment has not been fully elucidated. It highlights treatment options and their limitations and provides direction for future investigative efforts to aid in the treatment of these severe infections. While ampicillin plus ceftriaxone has emerged as a preferred treatment option mortality rates continue to be high and from a safety standpoint ceftriaxone unlike other cephalosporins promotes colonization with vancomycin resistant-enterococci due to high biliary concentrations. More research is needed to improve patient outcomes from this high-mortality disease.