Many accomplishments of public health can be cited, yet public health professionals face unprecedented challenges and opportunities in the coming decades. To assist public health practitioners, researchers, and educators in preparing for current and future changes affecting the population’s health, the authors describe several important “macrolevel” trends. These trends include: the aging of the population, changing patterns in the U.S. racial/ethnic composition, changes in health care delivery systems, the explosion of information technologies, changing needs in the public health work force, the growth in health-related partnerships, and anti-government sentiment and polarization. A series of implications for each of the major trends is provided. It may be important for public health leaders and policy makers to take these trends and implications into account as they plan and prioritize future approaches to disease prevention and health promotion.