This review tracks the evidence and associated recommendations and guidelines for optimal levels of physical activity for health benefit. In the 1950s, early epidemiological studies focused on the increased risk of cardiovascular disease and all-cause mortality associated with sitting at work. The period from the mid-seventies to the turn of the century saw an initial focus on the health benefits of vigorous exercise give way to mounting evidence for the benefits of moderate-intensity physical activity. As daily energy expenditure in most domains of human activity (travel, domestic and occupational work, and leisure) continues to decline, early 21st century researchers are starting to turn full circle, with a rekindling of interest in the health effects of sedentary behaviour at work, and indeed in the balance between activity and sedentariness in all aspects of daily life.