The traditional method of treating most human diseases is to direct a therapy against targets in the host patient, whereas conventional therapies against infectious diseases are directed against the pathogen. Unfortunately, the efficacy of pathogen-oriented therapies and their ability to combat emerging threats such as genetically engineered and non-traditional pathogens and toxins have been limited by the occurrence of mutations that render pathogen targets resistant to countermeasures. Our work shows that host proteins that are exploited by pathogens (Host Proteins Exploited by Pathogens; HPEPs) contribute to the severity of exposure to pathogenic agents. We find that pathogens recruit HPEPs to bind to, enter, reproduce in, exit from, and kill host cells. Thus, HPEPs are potential targets for therapies. This presentation will discuss examples of our drug discovery efforts to identify host-oriented therapies.