New proteomic technologies that utilize multiplexing to increase sample throughput and enrich datasets as compared to individual proteomic experiments are increasingly being used for biomarker discovery and other applications. Our work has centered on using these proteomic technologies in the study of host-pathogen interactions. We have studied both the pathogen proteomes and host proteomes following response to these pathogens in human and other animal systems. This presentation will show our work with 2-D DIGE, SELDI-MS, and protein arrays in an effort to better understand these systems and discover new countermeasure targets against these human and other animal pathogens. Our work on the plague bacterium, Yersinia pestis, its proteome under diverse conditions and diverse host response models to this pathogen will be highlighted. The presentation will also showcase key advances in the proteomics field that have helped to capitalize on these multiplexed technologies.