Microbial risk assessment is emerging as a new discipline in risk assessment. A systematic approach to microbial risk assessment is presented that employs data analysis for developing parsimonious models and accounts formally for the variability and uncertainty of model inputs using analysis of variance and Monte Carlo simulation. The purpose of the paper is to raise and examine issues in conducting microbial risk assessments. The enteric pathogen Escherichia coli O157:H7 was selected as an example for this study due to its significance to public health. The framework for our work is consistent with the risk assessment components described by the National Research Council in 1983 (hazard identification; exposure assessment; dose-response assessment; and risk characterization). Exposure assessment focuses on hamburgers, cooked a range of temperatures from rare to well done, the latter typical for fast food restaurants. Features of the model include predictive microbiology components that account for random stochastic growth and death of organisms in hamburger. For dose-response modeling, Shigella data from human feeding studies were used as a surrogate for E. coli O157:H7. Risks were calculated using a threshold model and an alternative nonthreshold model. The 95% probability intervals for risk of illness for product cooked to a given internal temperature spanned five orders of magnitude for these models. The existence of even a small threshold has a dramatic impact on the estimated risk.