The relationship between itch and psyche is complex and bilateral. Increasing interest in itch and its associations with psyche is indicated by the abundance of experimental and clinical articles published in this field. This review covers the pathogenesis of itch, associations with stress, the contagiousness of itch, psychological and psychiatric aspects related to itch, and the burden of itch with respect to impairment of health-related quality of life and stigmatization. Beginning from embryological development, skin and psyche are closely related to physiological state regardless of age. Altering the homeostasis of one of these components impacts on the other, thereby substantiating that the relationship between itch and psyche is bilateral. Itch has a complex pathogenesis, which involves the peripheral and central nervous systems, as well as various inflammatory mediators. This paper reviews key aspects of itch pathogenesis, relevant associations with stress, the contagiousness of itch, psychological and psychiatric considerations related to itch, and the burden of itch with respect to impairment of health-related quality of life (HRQoL) and stigmatization. Despite the fact that itch-psyche associations still pose many questions, current knowledge supports the role of a holistic, interdisciplinary approach to these patients in order to improve their well-being.