Purpose: The prevalence of obesity has reached epidemic proportions in many countries around the world. However, the genetic and environmental factors contributing to obesity are incompletely understood. Methods: We reviewed studies relating to the regulation of energy balance and how these factors may contribute to the development of obesity. Results: Although it is widely believed that genetics contribute significantly to the variability in body fatness, the available data do not support a role for defects in resting metabolic rate, substrate metabolism, dietary induced thermogenesis, or the energy cost of physical activity as significant causes of obesity. Furthermore, it is safe to say that the human genotype has not changed substantially over the past two to three decades. Data from several national surveys indicate that over the past few decades, there has been either a slight increase or a very modest decline in total energy and fat intake. This suggests that decreases in physical activity are a major contributing factor. Participation in leisure time physical activity is low but has remained relatively constant. However, an increased reliance on technology has substantially reduced work-related physical activity and the energy expenditure required for daily living. Conclusion: The most likely environmental factor contributing to the current obesity epidemic is a continued decline in daily energy expenditure that has not been matched by an equivalent reduction in energy intake. Because daily energy expenditure is decreasing, it is difficult for most people to restrict intake to meet energy requirements, and more and more people are becoming obese. Thus, increasing physical activity may be the strategy of choice for public health efforts to prevent obesity.