In 2004, the Women's Sports Foundation published the first edition of "Her Life Depends On It" (Don Sabo, Kathleen E. Miller, Merrill J. Melnick, and Leslie Heywood). At that time, it was clear that evidence-based research confirmed that regular physical activity and sport provides the critical foundation, in no small part, that allows girls and women to lead healthy, strong, and fulfilled lives. Now, five years later, "Her Life Depends On It II", provides an updated, and even more comprehensive, review of the existing research on the links between sports and physical activity and the health and well-being of American girls and women. This expanded review of existing research and health information is co-authored by a team of experts from several related disciplines, including epidemiology, exercise physiology, kinesiology, psychology, and sociology. Some key contributions of this new report include the following: (1) Research affirms, even more definitively than five years ago, that engagement in moderate and consistent levels of physical activity and sport for girls and women is essential to good health and well-being; (2) Although more research needs to be done, early studies examining the connections between physical activity and academic achievement show there is a positive relationship between the two in girls and women; (3) Females from lower economic backgrounds and females of color engage less in physical activity, have less access to sport and physical fitness programs, and suffer negative health consequences as a result; and (4) Emerging research in prevention and training practices show that gender-conscious approaches to physical training and conditioning for female athletes help to reduce the likelihood of anterior cruciate ligament (ACL) injuries and concussions. [Funding for this paper was provided by Gatorade. For the executive summary, see ED515840.]