Stress is a state of threatened homeostasis which mobilizes a composite spectrum of adaptive physiologic and behavioral responses with an aim to restore the homeostasis of the body. Stress is initiated by diverse type of adverse stimuli and responses to the stress include activation of the sympathetic nervous system, glucocorticoid secretion and emotional behaviours. Deregulation of the hypothalamic-pituitary-adrenal (HPA) axis is the hallmark of complex and interrelated changes triggered in the body in response to stress. Persistent stress is associated with different type of diseases such as anxiety, mood disorders and other neuropsychiatric diseases; skin diseases such as psoriasis, urticaria, alopecia areata and atopic dermatitis; gastrointestinal tract diseases such as peptic ulcer, irritable bowel syndrome; inflammatory disease such as rheumatoid arthritis; cardiovascular diseases such as cardiomyopathy and acute coronary syndrome. The present review discusses the role of different stress mediators and different type of diseases resulting due to stress.