Polycystic ovary syndrome (PCOS) is a heterogeneous disease with unknown etiology, a scientific challenge for researchers and is often a complex condition to manage for clinicians. Life exists by maintaining a complex dynamic equilibrium or homeostasis that is constantly challenged by intrinsic or extrinsic adverse forces, the stressors. Stress reactivity is markedly influenced by both pubertal maturation and the experience in the individual. For example, chronic stress destroys bodies, minds and lives. Chronic stress kills through suicide, violence, heart attack, stroke, and cancer. Much evidence suggests that women with PCO often at risk for secondary complications of this syndrome including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). The relation-ships between the psychological health aspects and the clinical characteristics of PCOS are not yet clear. In this review, we investigate the key roles of corticotrophin-releasing hormone (CRH) and norepinephrine (NE) in orchestrating the response to stress in women with PCOS.