Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in developed countries. Over the past decade there has been much focus on the role of inflammation in the pathogenesis of atherosclerosis; to this end, there is increasing research on inflammatory factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen (Fg). There is compelling evidence that physical activity (PA) and physical fitness (PF) protect against chronic disease. More recently, research has shown that exercise reduces CRP, IL-6, and Fg concentration in adults, and that this is often independent of adiposity. Although there are some data to suggest that this is similarly true for young people, there is inconsistency in the literature. The following review aims to illustrate what is known about the effects of PA and PF on inflammatory factors in young people aged 5–18 years.