Enterococci are the third most common nosocomial bloodstream pathogen and frequently are the causative pathogen(s) of intra-abdominal, genitourinary, surgical wound, endovascular, or other serious infections. In addition to a diverse spectrum of intrinsic and acquired antimicrobial resistance mechanisms, some strains of enterococci exhibit numerous virulence factors that facilitate mucosal adherence, tissue invasiveness, endovascular attachment, and inflammation production. However, the opportunistic nature of enterococcal infection coupled with animal models of experimental enterococcal and mixed infection have caused many to question the independent capacity of this organism to incite severe sepsis or septic shock. Despite evidence suggesting that this organism possesses low intrinsic virulence, observational and interventional trials of enterococcal bacteremia and sepsis strongly support the notion that Enterococcus is capable of promulgating sepsis as a solitary or copathogen with more serious sequelae in the immunocompromised hosts. Monomicrobial enterococcal bacteremia appears to be increasing during the glycopeptide-resistant era, which bolsters the notion that pure enterococcal sepsis is a real entity.