Abstract: Depression is a common neuropsychiatric disorder, marked by depressed mood for at least two weeks. The World Health Organization predicts that depression will be the number one leading cause of disease and injury burden by 2030. Clinical treatment faces at least three serious obstacles. First, the disease mechanism is not fully understood and thus there are no effective ways to predict and prevent depression and no biological method of diagnosis. Second, available antidepressants are based on monoamine mechanisms that commonly have a long delay of action and possibly cause a higher risk of suicide. Third, no other antidepressant mechanisms are available, with fast action and few side effects. Unfortunately, several decades of research based on rodent models of depression have not been successful in resolving these problems, at least partially due to the huge differences in brain function between rodents and people. Tree shrews are the closest sister to primates, and brain functions in these species are closer to those of humans. In this review, we discuss a tree shrew model of depression with social defeat etiology and aspects of construct, face and predicted validity of an animal model. Although a tree shrew model of depression has long been ignored and not fully established, its similarities to those aspects of depression in humans may open a new avenue to address this human condition.