Cancer survival is associated with considerable physical and psychosocial burden. Broadly accessible, nonpharmacologic measures that may extend disease-free survival, limit comorbid disease, and enhance quality of life are required. Sedentary behavior (too much sitting) is now understood to be a health risk that is additional to, and distinct from, the hazards of too little exercise. Of particular note, it is associated with adiposity, insulin resistance, and markers of inflammation. Therefore, it is plausible that sedentary behavior may contribute to adverse cancer outcomes (disease progression, recurrence, or death) and to the development of comorbid chronic disease. Initial studies indicate that cancer survivors spend two-thirds of their waking hours sitting. Among colorectal cancer survivors, sedentary behavior may contribute to all-cause and disease-specific mortality, weight gain, comorbid cardiovascular disease, and diminished quality of life. There is a need for dose-response evidence, and for a broader understanding of the underlying mechanisms by which prolonged sitting time may affect cancer survivors' health. Cancer 2013;119:1928–1935. © 2013 American Cancer Society.