Acne is one of the most common skin disorders. It is a multifactorial and complex disease, originating in the pilosebaceous follicle where a hereditary background, androgens, skin lipids, disorders of keratinization, inflammatory signaling, and regulatory neuropeptides seem to be mainly involved. Even though emotional stress has long been suspected to trigger or exacerbate acne, its influence on acne severity has been mostly underestimated until recently when studies have brought new data about the different mechanisms and possible factors involved in this interaction. A point to note is that there have been relatively few studies examining stress as a possible cause of acne or acne exacerbation; more studies have focused on stress and mental health problems occurring as a result of acne. In this review, we have tried to identify the underlying mechanisms that link stress to acne according to the latest scientific findings, and we summarize this perplexing connection. The basis for the association between emotional stress and the onset or exacerbation of acne is in several cutaneous neurogenic factors which interact with a pathogenic cascade in acne. This bidirectional intimate relationship of the skin and the mind emphasizes the importance of a holistic and interdisciplinary approach to caring for patients with acne that involves not only dermatologists but also psychologists and psychiatrists.