The NRC report Science and Decisions: Advancing Risk Assessment made several recommendations to improve chemical risk assessment, with a focus on in-depth chronic dose–response assessments conducted by the U.S. Environmental Protection Agency. The recommendations addressed two broad elements: improving technical analysis and utility for decision making. To advance the discussions in the NRC report, in three multi-stakeholder workshops organized by the Alliance for Risk Assessment, available and evolving risk assessment methodologies were considered through the development and application of case studies. A key product was a framework (http://www.allianceforrisk.org/Workshop/Framework/ProblemFormulation.html) to guide risk assessors and managers to various dose–response assessment methods relevant to a range of decision contexts ranging from priority setting to full assessment, as illustrated by case studies. It is designed to facilitate selection of appropriate methodology for a variety of problem formulations and includes a variety of methods with supporting case studies, for areas flagged specifically by the NRC committee for consideration – e.g., susceptible sub-populations, population variability and background. The framewok contributes to organization and communication about methodologies for incorporating increasingly biologically informed and chemical specific knowledge into dose–response analysis, which is considered critical in evolving fit-for-purpose assessment to address relevant problem formulations.