Recently, it was suggested that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic roles in depression. The aim of this review is to discuss the novel potential pharmacological effects of RES on depression. We first consider the pathophysiology of depression and then review the potential antidepressant effects of RES. Apart from the alternation of the monoaminergic system and the molecular markers related to depression, RES might exert an antidepressant-like effect through modulating the HPA axis, BDNF and synaptic vesicle proteins, inflammatory cytokines and oxidative stress, and thyroid hormones. Consumption of RES may represent an alternative strategy to delay the onset and progression of depression, and depressive-like symptoms through multiple pharmacological activities.