Cigarette smoking and exposure to secondhand smoke kill an estimated 443,000 people in the United States each year. For every smoker who dies from a smoking-attributable disease, another 20 live with a serious smoking-related disease. Smoking costs the United States $96 billion in medical costs and $97 billion in lost productivity each year. Despite progress in reducing tobacco use, one in five U.S. high school students and adults still smoke. These statistics reflect a legacy of millions of lives prematurely lost from tobacco use, reflecting a tragic public health history. Before the introduction of the modern mass-marketed cigarette in the late 1800s, lung cancer was rare. In stark contrast, lung cancer is now this nation's leading cause of cancer death among both men and women, killing an estimated 160,000 people in the United States each year. The dramatic rise in smoking in the 20th century prompted a prominent historian to refer to that time period as “The Cigarette Century.” But the 21st century has witnessed a convergence of public attitudes and political support that creates an unprecedented opportunity for the United States. On June 22, 2009, President Obama signed into law historic legislation granting the U.S. Food and Drug Administration (FDA) authority to regulate tobacco products to protect the public health. In reviewing the need to accelerate progress in tobacco control and announcing the new FDA regulations restricting tobacco marketing to children on March 19, 2010, Kathleen Sebelius, Secretary of Health and Human Services, stated, “This needs to be a national effort. The lesson that we should take from the successes of the past 50 years is not that progress sis inevitable. It's that saving lives and reducing health costs is possible, but only if we pursue an aggressive policy agenda.” On March 23, 2010, President Obama signed into law historic health insurance reform legislation, the Patient Protection and Affordable Care Act (Affordable Care Act). As noted by Secretary Sebelius in testimony before the U.S. House of Representatives on April 21, 2010, the law creates a new Prevention and Public Health Fund that will provide a significant investment to “allow HHS to expand and sustain prevention, wellness, and public health programs to improve the health of the nation and help restrain health care costs.” The law also specifically expands smoking cessation coverage now for pregnant Medicaid beneficiaries and enhances prevention initiatives in 2013 by offering financial incentives to States to provide optional services that encourage healthy behaviors by Medicaid beneficiaries. The U.S. Department of Health and Human Services (HHS) can leverage this historic moment to launch a new chapter to end tobacco-related suffering and death. This strategic action plan proposes a comprehensive approach designed to mobilize HHS's expertise and resources in support of proven, pragmatic, achievable interventions that can be aggressively implemented not only at the federal level, but also within states and communities. The activities described in the plan are meant to serve as a guideline for future development, are conditional, and are subject to the availability of resources. Implementing the strategic actions in this plan can enable the United States to meet the Healthy People objective of reducing the adult smoking rate to 12%. Together, the recommended actions offer an historic opportunity to accelerate our efforts to end the tobacco problem.