This chapter reviews the findings from epidemiologic studies of the associations of physical activity with gynecologic cancers, including those of the endometrium, ovaries, and cervix, and the biologic mechanisms mediating the associations. The epidemiologic evidence to date suggests that physical activity probably protects against endometrial cancer, with a risk reduction of about 20-30% for those with the highest levels of physical activity compared to those with the lowest levels, and that light to moderate physical activity including housework, gardening, or walking for transportation may reduce risk. The role of physical activity in ovarian cancer development remains uncertain, as findings from these studies have been inconsistent with about half the studies suggesting physical activity modestly decreases risk and about half the studies suggesting no association. A recent meta-analysis of studies examining recreational physical activity with ovarian cancer risk estimated a 20% reduced risk for the most active versus least active women. There is mounting evidence that sedentary behaviors such as sitting time probably increase risk of endometrial and ovarian cancers. Overall, there is insufficient evidence to draw a conclusion on a possible role of physical activity in the development of cervical cancer, although a modest influence on risk is possible through effects on sex steroid hormones and immune function. The biologic evidence provides strong support for a protective role of physical activity on cancer of the endometrium, and moderate support for cancer of the ovaries, as these cancers have a strong hormonal etiology. The more established biologic mechanisms that are supported by epidemiologic and experimental data involve endogenous sex hormone levels, insulin-mediated pathways, and maintenance of energy balance.In this chapter, we will discuss the evidence for an association of physical activity with gynecologic cancers including those of the endometrium, ovaries, and cervix. Cancers of the endometrium and ovaries have a strong hormonal etiology (Risch 1998; Kaaks et al. 2002; Lukanova and Kaaks 2005), and physical activity has been postulated as a potential modifiable risk factor for prevention of these cancers because it can influence circulating hormone levels, energy balance, and insulin-mediated pathways that are thought to be important mediators underlying the associations. Few studies have evaluated the association of physical activity with cervical cancer because the main causal factor is infection with certain types of human papillomavirus (HPV), although other hormonal and immune factors are also thought to play a role (Smith et al. 2003; Waggoner 2003). We review the findings from epidemiologic studies that have examined the associations of physical activity with gynecologic cancers, and the biologic mechanisms that might mediate the associations.