In 1995 we published a review describing the scientific and legal bases for the GRAS assessment program for flavor ingredients sponsored by the Flavor and Extract Manufacturers Association of the United States (FEMA) [Hallagan, J.B., Hall, R.L., 1995. FEMA GRAS - A GRAS assessment program for flavor ingredients. Regulatory Toxicology and Pharmacology 21, 422]. This review provides new information related to flavor safety assessment and regulation and is intended to complement our previous report. The FEMA GRAS assessment program is the most extensive and longest running industry-sponsored GRAS program and has established a sound record of scientific rigor and transparency. In this review, in addition to providing general information on the topics of flavor safety assessment and regulation, we explore the effects of recent developments on the four pillars of the FEMA GRAS assessment program: (1) general recognition; (2) among experts qualified by scientific training and experience to evaluate safety; (3) through scientific procedures; (4) under the conditions of intended use in food. We conclude that developments since our last review in 1995 have further strengthened the FEMA GRAS assessment program allowing it to maintain its global leadership role in the safety assessment of flavor ingredients.