There is increasing interest in the development of a microbial risk assessment methodology for regulatory and operational decision making. This document presents a methodology for assessing risks to human health from pathogen exposure using a population-based model that explicitly accounts for properties unique to an infectious disease process, specifically secondary transmission and immunity. To demonstrate the applicability of this risk-based method, numerical simulations were carried out for a case study example in which the route of exposure was direct consumption of biosolids-amended soil and the pathogen present in the soil was enterovirus. The output from the case study yielded a decision tree that differentiates between conditions in which the relative risk from biosolids exposure is high and those conditions in which the relative risk from biosolids is low. This decision tree illustrates the interaction among the important factors in quantifying risk. For the case study example, these factors include biosolids treatment processes, the pathogen shedding rate of infectious individuals, secondary transmission, and immunity. Further refinement in methods for determining biosolids exposures under field conditions would certainly increase the utility of these approaches.