Objective: This narrative review updates evidence from the last 10 years on physical activity (PA) and the primary prevention of cardiovascular disease, diabetes, and cancer in women. Methods: A literature search was conducted to identify prospective cohort studies published from January 1997 to February 2006. Results: There were significant reductions in risk in 12 of 17 studies of cardiovascular outcomes (risk reductions ranging from 28% to 58%), in seven of eight studies of diabetes (14% to 46%), in seven of ten studies of breast cancer (11% to 67%), in two of two studies of endometrial cancer (68% to 90%), and in one of three studies of colorectal cancer (31% to 46%). There was mixed evidence for PA preventing gestational diabetes (three studies) and a range of other cancers (13 studies). Protective benefits for cardiovascular disease and diabetes were reported with as little as 60 minutes of moderate-intensity physical activity per week (240 Metabolic Equivalent (MET) minutes or 4 MET hours), with walking and moderate-intensity physical activity providing risk reductions comparable to those for the equivalent energy expenditure from more vigorous-intensity physical activity. Conclusions: There is strong evidence of a role for PA in the primary prevention of cardiovascular disease, diabetes, and some cancers in women. There was no evidence of additional health benefits from vigorous-intensity PA, over and above those achieved from walking or moderate-intensity PA. This may be because, in most studies, there was limited reporting of vigorous PA by women. For some health outcomes, the amount of PA required for health benefits in middle-aged and older women might be lower than current national recommendations.