This article describes the prevalence of risky behaviors known to be associated with increased cancer morbidity and mortality among Ohio Appalachian adults. These behaviors, or risk factors, include: 1) tobacco use; 2) energy imbalance (involving poor diet, obesity, and physical inactivity); and 3) sexual behaviors. We report current estimates of the prevalence of these behaviors among Ohio Appalachian adult residents and review social, psychological, and biological variables associated with these risky behaviors. We also present recent empirical studies that have been completed or are in progress in Ohio Appalachia. Finally, we discuss how these studies help bridge well-documented gaps in the literature.