Cortisol has major impacts upon a range of physiological homeostatic mechanisms and plays an important role in stress, anxiety and depression. Although traditionally described as being solely synthesised via the hypothalamic-pituitary-adrenal (HPA) axis, recent animal and human studies indicate that cortisol may also be synthesised via a functionally-equivalent 'peripheral' HPA-like process within the skin, principally within hair follicles, melanocytes, epidermal melanocytes and dermal fibroblasts. Current data indicate that basal levels of cortisol within hair vary across body regions, show diurnal variation effects, respond to the onset and cessation of environmental stressors, and may demonstrate some degree of localisation in those responses. There are conflicting data regarding the presence of variability in cortisol concentrations across the length of the hair shaft, thus challenging the suggestion that hair cortisol may be used as a historical biomarker of stress and questioning the primary origin of cortisol in hair. The need to comprehensively 'map' the hair cortisol response for age, gender, diurnal rhythm and responsivity to stressor type is discussed, plus the major issue of if, and how, the peripheral and central HPA systems communicate.