Since the advent of antibiotics in the 1920s, these drugs have saved millions of people from diseases such as pneumonias, healthcare associated infections, and foodborne illnesses. However, the continued use of antibiotics has led to several unintended consequences, including disruption of the indigenous beneficial gut bacteria and a rise in antibiotic-resistant bacteria. The Centers for Disease Control and Prevention (CDC) estimates that 23,000 deaths are caused by antibiotic-resistant bacteria each year in the United States, and these organisms constitute a growing problem worldwide. Vancomycin-resistant enterococci (VRE), which have been classified as a serious threat by the CDC, are responsible for 20,000 U.S. infections annually. The inability to treat these infections with common antibiotics necessitates the development of alternative methods of intervention. The objective of my investigation is to develop and characterize an effective bacteriophage therapy against VRE, including both vancomycin-resistant E. faecalis and E. faecium. I have modified a mouse a model of VRE infection, which uses ampicillin to disrupt the normal gut microbiota to allow VRE to colonize and persist in the host. I have collected several naturally occurring phage isolates against a range of VRE strains. Using virulent phages, I designed a cocktail with high activity against the E. faecalis strain used to infect mice. This cocktail was administered to VRE colonized mice to study its efficacy. Preliminary data suggests that a phage cocktail could be successfully utilized to decolonize VRE-infected mice. This treatment will be compared with a standard antibiotic intervention, linezolid, for differences in efficacy as well as differences in their effects on the microbiota. These bacteriophage therapy investigations will have a significant impact on a largely understudied field and contribute to solving the antibiotic-resistant bacteria problem.