Many environmental challenges facing society today, such as climate change and integrated water management, have been described as "wicked problems" due to their biological, physical, and social complexity. Wicked problems extend across media such as air, land, and water; across political jurisdictions and landscape boundaries; and across traditional policy arenas. Traditional policy approaches that are media-specific, rely on single agencies for implementation, and that do not effectively engage stakeholders and partners outside of government are generally ineffective in addressing these issues. The management of toxic chemicals is a classic "wicked problem." Existing toxics policies often exacerbate the "wicked" nature of this issue by ignoring its inherent complexity and the need to bridge across agencies, jurisdictions, and constituencies to effectively manage these substances. Current US policies make it difficult to gather sufficient information to assess the environmental and health impacts of the thousands of chemicals in use. Lack of incentives for industry to invest in safer alternatives has also created a gap between the need for safer chemical alternatives and development of safer technologies, processes, or products. This article explores how policy strategies that foster cross-agency coordination, engage stakeholders in policy development and implementation, and represent a more systems-oriented, holistic approach may be more effective in addressing such complex wicked problems. While federal action is needed to avoid a regulatory "race to the bottom," there are also opportunities for states to encourage the development and adoption of safer alternatives to chemicals of concern.