The worldwide ratio of Enterococcus faecalis-Enterococcus faecium infections is currently changing in favor of E. faecium. Intrinsic and acquired antimicrobial resistance traits of this latter species can explain this evolution as well as the diffusion of hospital-adapted strains belonging to the clonal complex CC17. Like other enterococci, E. faecium is naturally resistant to cephalosporins and aminoglycosides (at low level). Because of its high genome plasticity, it can also acquire numerous other resistances. It is noteworthy that most modern isolates of E. faecium are highly resistant to ampicillin while a non-negligible proportion of them (depending on geographical locations) are resistant to glycopeptides (especially in the USA). Even if resistance to newer antimicrobial agents (linezolid, daptomycin, tigecycline) is still uncommon, some clinical isolates with reduced susceptibility or resistance have already been reported and better understanding of resistance mechanisms is needed for prediction and prevention of their dissemination.