There is growing awareness of the health implications of fact that infectious agents often do not act independently; rather their disease potential is mediated in diverse and significant ways by their relationships with other pathogens. Pathogen-pathogen interaction (PPI), for example, impacts various virulence factors in human infection. Although still in its infancy, the study of PPI, a form of epidemiological synergism, is emerging as an important arena of new research and new understanding in health and clinical care. The aims of this paper are to: 1) draw attention to the role of PPI in human disease patterns; 2) present the syndemics model as a biosocial approach for examining the nature, pathways, contexts, and health implications of PPI; and 3) suggest the utility of this approach to PPI. Toward these ends, this paper (a) reviews three of case examples of alternative PPIs, (b) describes the development and key concepts and components of the syndemics model with specific reference to interacting infectious agents, (c) contextualizes this discussion with a brief review of broader syndemics disease processes (not necessarily involving infections disease), and (d) comments on the research, treatment and prevention implications of syndemic interaction among pathogens.