The substantial health and economic costs of excessive alcohol consumption make its reduction a major public health and economic concern. The Community Preventive Services Task Force, based on a systematic review of the research literature, concluded that restricting alcohol retail outlet density through local land use and zoning regulations is an effective strategy for reducing these costs. Yet the implementation of the Task Force's recommendation is limited by state pre-emption, which determines the extent to which states allow local government to adopt policies and enact legislation. This article summarizes the state pre-emption doctrine, its status in the 50 states pertaining to alcohol retail outlet density regulation, and findings from state legal analyses conducted in six states. Data reflect state laws in effect as of January 1, 2012. Analyses were conducted during the 2012 calendar year. An examination of relevant state laws found five distinct pre-emption categories: exclusive state licensing, exclusive state licensing and concurrent local zoning, joint licensing, exclusive local licensing, and a mixed system. The analysis demonstrated wide variability across the states, ranging from exclusive state pre-emption to broad state delegation of authority to local governments. Pre-emption is applied differentially in many states based on retail outlet characteristics. In many cases, state pre-emption laws are ambiguous in terms of their application, leading to inconsistent and confusing court interpretations. Reforms targeting the adverse impact of state pre-emption on alcohol retail outlet density have the potential for reducing the harm associated with excessive alcohol consumption. State and local public health departments can support such reforms by implementing educational, analytic, monitoring, and technical assistance activities.