Significant public health problems associated with methamphetamine (MA) production and use in the United States have emerged over the past 25 years. Although the popular press (Newsweek, Aug 8, 2008), has called MA “America’s Most Dangerous Drug” there has been considerable controversy about the size of the problem. Epidemiological indicators have given a mixed picture. National surveys of the adult U.S. population and school-based populations have consistently been used to support the position that MA use is a relatively minor concern (NSDUH, 2006; Johnston & O’Malley, 2007). However, many other data sources, including law-enforcement groups, welfare agencies, substance abuse treatment program admission data, data on criminal justice populations, and state/county executives indicate that MA is a very significant public health problem for many communities throughout much of the country (NDIC, 2007b; NACO, 2005, 2006; NIDA CEWG, 2007). In this article, we describe (1) the historical underpinnings of the MA problem, (2) trends in the epidemiological nature of the MA problem, (3) key subgroups at risk for MA problems, (4) the health and social factors associated with MA use, (5) interventions available for addressing the MA problem, and (5) lessons learned related to the MA problem.