The emergence of resistance against multiple antibiotics and the increasing frequency with which Enterococcus faecalis and Enterococcus faecium are isolated from hospitalized patients underscore the necessity for a better understanding of the virulence mechanisms of this pathogen and the development of alternatives to current antibiotic treatments. The genetic plasticity of enterococci and their ability to rapidly acquire and/or develop resistance against many clinically important antibiotics and to transfer these resistance determinants to other more pathogenic microorganisms makes the search for alternative treatment and preventive options even more important. A capsular polysaccharide antigen has recently been characterized that is the target of opsonic antibodies. A limited number of clinically relevant serotypes exist, and the development of an enterococcal vaccine based on capsular polysaccharides may improve our ability to prevent and treat these infections. Additional enterococcal surface antigens, including ABC transporter proteins and other virulence factors, such as aggregation substance (AS), may also be useful targets for therapeutic antibodies.