Cellular senescence has emerged as a biological response to two major pathophysiological states of our being: cancer and aging. In the course of the transformation of a normal cell to a cancerous cell, senescence is frequently induced to suppress tumor development. In aged individuals, senescence is found in cells that have exhausted their replication potential. The similarity in these responses suggests that understanding how senescence is mediated can provide insight into both cancer and aging. One environmental factor that is implicated in both of these states is tissue hypoxia, which increases with aging and can inhibit senescence. Hypoxia is particularly important in normal physiology to maintain the stem cell niche; but at the same time, hypoxic inhibition of an essential tumor suppressor response can theoretically contribute to cancer initiation.