This chapter discusses two unique environmental influencers of the genetic regulation of activity and potential mechanisms through which each are hypothesized to regulate activity. Prior to genetics being considered a regulator of physical activity, work from the early 1920s and 1930s suggested that daily activity was controlled through biological mechanisms. Wang, Richter, and colleagues investigated the relationship between the female reproductive cycle and wheel-running behavior in rodents. The harmful consequences of endocrine-disrupting chemicals (EDCs) on human health have been widely studied over the past few decades and growing evidence has supported that man-made chemicals contribute to adverse health effects on humans and wildlife. In short, EDCs are ubiquitous in environment with exposure ranging from personal care products to food packaging and processing. Disruption in hormone levels from EDC exposure can cause a variety of physiological problems that vary in severity and differ by sex, few studies have examined the direct relationship between EDC exposure and physical activity.