Three of the major causes of death are cardiovascular disease, diabe- res, and cancer. These diseases are linked to the presence of a low-grade chronic inflammation as shown by elevated blood levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-o). What is important to know is that doing moderate-to-vigorous physical activity on a regular basis (e.g., 3 to 5 d/wk) is associated with positive health outcomes, including a reduction in the risk of type 2 diabetes, heart disease and certain cancers. What is the connection between exercise and the reduced risk of these diseases? Until recently, little was known about the connection, but now it appears that it is muscle itself that brings about these favorable changes (11, 88, 101) over the past ten years, it has become clear that muscle is an endocrine organ that is, it produces small re signaling molecules called myokines (muscle cytokines) when it con- tracts. The number and types of these myokines continue to grow (106), indicating that muscle contraction plays a much larger role than simply getting us down the road. Some of these myokines act locally as autocrine agents to stimulate glucose uptake and increase fatty acid oxidation, and as paracrine agents to promote blood vessel growth in muscle However, other myokines are released into the blood so that they can act as hormones and affect a variety of tissues and organs. For example, some myokines can increase liver production of glucose and stimulate triglyceride breakdown in adipose tissue to provide free fatty acids for fuel (11, 88, 101).