Immunology comprises a multifaceted research agenda that has developed around the clinical challenges of host defense, transplantation, autoimmunity, tumor immunology, and allergy. The physiological processes mediating these clinical problems designate the immune system, which, in turn, is understood in terms of establishing and maintaining organismal identity. While immunology as a science has been defined as the “science of self/nonself discrimination” (Golub and Green 1991), from a philosophical point of view, immunology is the science concerned with those mechanisms defining the identity of the organism. This more expansive definition allows for conceiving immune processes in their broadest biological context, namely, in addition to defensive and restorative processes, the immune system also may be understood as engaged in information processing and cognition; active exchange with the environment to allow for benign intercourse; and tolerance for symbiotic relationships constitutive of an organism conceived as a complex holobiont. Thus two general orientations vie for dominance: (1) the traditional biomedical concern with host defense emphasizes the insularity of the organism and immunity in service to its protection; and (2) immunity in its full ecological context—internal and external—mediates the organism’s dynamic identity in dialectical exchange with its environment. In either case, cognition—its models, metaphors, and organization—serves as the central issue pertinent to philosophical considerations of biological identity, individuality, organism, and agency.