Social stress is known to be involved in the etiology of central nervous disorders such as depression. In recent years, animal models have been developed that use chronic stress to induce neuroendocrine and central nervous changes that might be similar to those occurring in the course of the development of depressive disorders. The present review gives a summary of observations made in the tree shrew chronic social stress model. During periods of daily social stress, male tree shrews develop symptoms that are known from many depressed patients such as persistent hyperactivities of both the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, disturbances in sleeping patterns, and reduced motor activity. Moreover, various physiological parameters indicate an acceleration of the over all metabolic rate in socially stressed tree shrews. Some of these parameters can be renormalized by antidepressants thus supporting the view of the tree shrew social stress paradigm as model for major depression. In the brains of socially stressed animals, monoamine receptors show dynamic changes that reflect adaptation to the persistent monoaminergic hyperactivity during periods of chronic stress. In addition to the changes in neurotransmitter systems, there are structural changes in neurons, e.g., retraction of the dendrites of hippocampal pyramidal neurons. Together, these processes are suggested as a cause of behavioral alterations that can be counteracted by antidepressants in this naturalistic social stress model.