Cumulative risk assessment (CRA) is an emergent tool for organizing and analyzing scientific information to examine, characterize, and possibly quantify adverse health outcomes from combined effects of exposure to diverse environmental factors, including both chemical and nonchemical stressors. This article examines the implementation of effects-based CRA, which emphasizes evaluating health risks in a defined community or population, as opposed to stressor-based approaches, which focus on determining health risks for a defined set of stressors. It discusses the concept of vulnerability-based CRA as a potentially useful alternative, reviews the conceptual constructs that underpin CRA, surveys the diversity of methods available for putting effects-based principles into practice, identifies impediments hindering practical applications, and examines ways to make effects-based CRA more feasible.