The market for functional products, such as probiotics, is undoubtedly the fastest growing area of new food product development. This market introduces a new paradigm for food safety professionals: beneficial physiological effects beyond those of good nutrition without adverse effects. This specificity generates a need for new approaches in food safety evaluation. Conventional toxicology and safety evaluation alone is of limited value in the safety evaluation of probiotic microorganisms. Instead, a multidisciplinary approach is necessary, involving the contributions of pathologists, geneticists, toxicologists, immunologists, gastroenterologists, and microbiologists. In the case of new products, the objective is to produce products that are at least as safe as conventional counterparts regardless of potential health benefits. In the case of existing strains, the history of safe use criterion is very much associated with being able to detect, enumerate and characterize strains to ensure consumers have been ingesting the same organism throughout the claimed exposure period.