Increased epidemiological evidence over the past few years has shown excessive sitting to be a health risk even if recommendations for physical activity are fulfilled. Sitting is an independent health risk for two reasons: sitting and physical activity exhibit poor correlation, and an increase in physical activity does not contribute to all mechanisms underlying the health risks of sitting. During sitting, muscular passivity increases insulin resistance and influences the transport and oxidation of fatty acids in muscular tissue, and acute exercise is not sufficient to restore all changes. Accordingly, adequate everyday physical activity seems to be important for maintaining the signaling pathways affecting insulin sensitivity.