The current view of the manner in which (n-3) polyunsaturated fatty acids (PUFA) affect the immune system is centered on their ability to alter cytokine production and secondarily to diminish eicosanoid biosynthesis. The purpose of this article is to review the evidence that (n-3) PUFA affect host infectious disease resistance. Although there have been a few human clinical trials involving (n-3) PUFA and human infectious disease, the data are equivocal and the study designs confounded by the simultaneous inclusion of other immunonutrients (i.e., arginine and nucleotides) with the (n-3) PUFA. Thus, this review focuses on animal feeding trials that include an in vivo challenge of the host with a live infectious agent. Host survival and pathogen clearance are the most common end points measured in these studies. The data suggest that (n-3) PUFA can both improve and impair host resistance to a number of pathogens. However, the data are still quite limited in breadth and depth. For those pathogens for which data exist, the number of published studies in general does not exceed two or three. Emphasis is placed on defining important microbiological and immunological differences in various host-pathogen interactions that might help explain the incongruity in the findings published to date. The authors believe that direct examination of (n-3) PUFA on human infectious disease resistance is warranted.