Bacteriophage therapy is a promising treatment for periprosthetic joint infections (PJIs), particularly given these agents have innate abilities to degrade the biofilm matrix and lyse bacteria within. However, many aspects of this therapy are poorly understood causing treatments to lack uniform effectiveness and reproducibility, which is in part a consequence of several inherent limitations to using bacteriophages to treat PJI. Herein, these limitations are discussed as are additional translational research that needs to be conducted to advance this therapeutic. These include determining if bacteria causing PJIs are polyclonal, consequences of bacteriophage attachment receptor phenotypic variations and ramifications of bacteriophage activity when bacteria interact with in vivo macromolecules. Only with the realization of the current limitations and subsequent knowledge gained from translational research will the potential of bacteriophages to reduce the morbidity and mortality in PJI be fully elucidated.