Challenges and solutions toward clinical application of phage therapy. Depicted are several of the major challenges and proposed solutions for the application of phage therapy. These include regulatory obstacles limiting phage cocktail application that may be addressed by the development of adaptive regulatory protocols; bacterial resistance can be addressed by a rational design of phage cocktails, co-administration with antibiotics, and synthetic alteration of phage structure; challenges related to bioavailability and immunogenicity could be addressed by engineering phage outer structures or phage encapsulation, (e.g., via PEGylation) making them less immunogenic, or through the development of oral routes of administration for gut microbiome modulation; safety challenges may be addressed by following cGMP regulations, pre-selecting phage strains and their co-administration with other antimicrobials