Viral and pathogen protein complexity is often limited by their relatively small genomes, thus critical functions are often accomplished by complexes of host and pathogen proteins. This requirement makes the study of host-pathogen interactions critical for the understanding of pathogenicity and virology. This review article discusses proteomic methods that offer an opportunity to experimentally identify and analyze the binding partners of a target protein and presents the representative studies performed with these methods. These methods divide into two classes: and . assays depend on bindings that occur outside of the normal cellular environment and include yeast two hybrids, pull-downs, and nucleic acid-programmable protein arrays (NAPPA). assays depend on bindings that occur inside of host cells and include affinity purification (AP) and proximity dependent labeling (PDL). Either or methods can be reliably used for generating protein-protein interactions networks but it is important to understand and recognize the limitations of the chosen methods when developing an interactomic network. In summary, proteomic methods can be extremely useful for interactomics but it is important to recognize the nature of the method when designing and analyzing an experiment.