Post-stroke depression is an important psychological consequence of ischemic stroke, and affects around one third of stroke patients at any time post-stroke. It has a negative impact on patient morbidity and mortality, and as such development of effective post-stroke recognition and treatment strategies are very important. There are several therapeutic strategies for post-stroke depression, including both pharmacological and non-pharmacological approaches. In this review, we present evidence regarding the underlying biology of post-stroke depression, commonalities between post-stroke depression and Major Depressive Disorder and explore several treatment approaches, including antidepressant therapy, psychotherapy, surgical therapy, electroconvulsive therapy, acupuncture, music therapy and natural products. Further experimental and clinical studies are required, particularly in emerging fields such as the role of nutraceuticals in the treatment of stroke.