The brain is a vital organ, susceptible to alterations under genetic influences and environmental experiences. Social isolation (SI) acts as a stressor which results in alterations in reactivity to stress, social behavior, function of neurochemical and neuroendocrine system, physiological, anatomical and behavioral changes in both animal and humans. During early stages of life, acute or chronic SIS has been proposed to show signs and symptoms of psychiatric and neurological disorders such as anxiety, depression, schizophrenia, epilepsy and memory loss. Exposure to social isolation stress induces a variety of endocrinological changes including the activation of hypothalamic–pituitary–adrenal (HPA) axis, culminating in the release of glucocorticoids (GCs), release of catecholamines, activation of the sympatho-adrenomedullary system, release of Oxytocin and vasopressin. In several regions of the central nervous system (CNS), SIS alters the level of neurotransmitter such as dopamine, serotonin, gamma aminobutyric acid (GABA), glutamate, nitrergic system and adrenaline as well as leads to alteration in receptor sensitivity of N-methyl-D-aspartate (NMDA) and opioid system. A change in the function of oxidative and nitrosative stress (O&NS) mediated mitochondrial dysfunction, inflammatory factors, neurotrophins and neurotrophicfactors (NTFs), early growth response transcription factor genes (Egr) and C-Fos expression are also involved as a pathophysiological consequences of SIS which induce neurological and psychiatric disorders.