The impact of depression on physical disability is undisputed. There is convincing evidence that depression increases the subsequent risk for physical disability and, in turn, physical disability results in increased depressive symptoms. Moreover, depression affects also the earlier stages of the disablement process (including functional limitation in mobility) and may accelerate the transitioning along the pathway to disability. Greater knowledge of the structure of this detrimental relationship and the underlying mechanisms should inform the clinical management of older persons at risk of physical decline and the development of effective interventions that break this downward spiral.