BACKGROUND: This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants. OBJECTIVES: Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. DISCUSSION: Superfund-relevant CECs can be characterized by specific attributes: They are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites. CONCLUSIONS: A need exists for a carefully considered and orchestrated expansion of programmatic and research efforts to identify, evaluate, and manage CECs of hazardous waste site relevance, including developing an evolving list of priority CECs, intensifying the identification and monitoring of likely sites of present or future accumulation of CECs, and implementing efforts that focus on a holistic approach to prevention.