The Wnt signaling pathway has been recognized as an important pathway, extending its function throughout the lifespan. Evidence suggests that dysfunctional Wnt signaling in the adult brain leads to aberrant neurogenesis, synaptogenesis, modulation of mature synapses and neurotransmitter release in the hippocampus. Due to the involvement of Wnt proteins in hippocampal functioning, altered Wnt signaling has been suggested to be an important factor in the pathophysiology of mood disorders. Interestingly, the effects of mood-stabilizing drugs are believed to work through interactions with Wnt molecules, and epigenetic mechanisms have been shown to interact with components of the Wnt pathway and impact mechanisms such as synaptic plasticity. This can affect learning and memory formation, in addition to various behavioral outcomes in individuals, when they are faced with stressful or conflict situations. This review will discuss the integrated role of Wnt signaling in the context of appropriate stress response, which is believed to be mediated by adult hippocampal neurogenesis and plasticity. Current knowledge regarding the role of Wnt signaling in mood disorders and antidepressant medication effect will be covered. Finally, the interplay between Wnt signaling and epigenetic mechanisms will be discussed along with their combined potential to impact neuroplasticity.