Immunotoxicity testing is used to provide safety assessment with the major objective being the avoidance of unacceptable risk of infectious or neoplastic disease. To this end, immunotoxicity testing has employed a variety of host resistance challenge models for measuring both host resistance to disease as well as immune function. This chapter provides an overview of those viral, bacterial, fungal, and parasitic host resistance models that are most commonly used in safety assessment. It also describes in more detail the bacterial challenge models that are employed to address specific host resistance and immune function issues.