Depression is one of the most prevalent and devastating psychopathologies humanity faces with no algorithmic cure based on the present pharmacotheraputic techniques and exclusively central approach to its pathogenesis and therapy. This book provides strong evidence that a comprehensive assessment of both the etiology and therapeutics of depression requires an integrative view of how affect and mood are modulated by both peripheral and central affective mechanisms. Specifically, sensorimotor stimulation via the five sensory modalities (vision, audition, olfaction, touch and gustation), as well as the motor system, is capable of modulating mood and depression. This means that, depending on several parameters, peripheral, bottom-up sensorimotor stimulation can have the diametrically opposite effects of alleviating or aggravating mood and depression in humans and animals. Moreover, depression, in turn, can modulate sensorimotor function mostly in the negative direction, impairing sensory processing, as well as motor behavior, further complicating the depressive state.