Chronic stress is an inextricable part of modern daily living; practically all human diseases, particularly cancer, are negatively affected by it. Numerous studies have shown that stressors, depression, social isolation, and adversity correlate with a worse prognosis for patients with cancer, with increased symptoms, early metastasis, and a shortened life span. Prolonged or very intense adverse life episodes are perceived and assessed by the brain and translated into physiologic responses mediated through relays to the hypothalamus and locus coereleus. This response triggers the activation of the hypothalamus-pituitary-adrenal axis (HPA) and the peripheral nervous system (PNS) with the secretion of glucocorticosteroids/epinephrine and norepinephrine (NE). These hormones and neurotransmitters affect immune surveillance and the immune response to malignancies by skewing immunity from a type 1 to a type 2 response; this process not only impedes the detection and killing of cancer cells but induces immune cells to facilitate cancer growth and systemic spread. It may be mediated by the engagement of norepinephrine to β-adrenergic receptors, which can be partially reversed by the administration of β-blockers.