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By its size and diversity, the cutaneous microbial flora is the second of the human body and there is a growing body of research showing its key role in cutaneous homeostasis. However, skin is also the first neuroendocrine organ and it is now demonstrated that bacteria can sense a multitude of human hormones and neurotransmitters. Then, besides of the intrinsic effect of their virulence factors on cutaneous neurogenic activity, recent data demonstrate that the virulence, invasion potential, and biofilm formation activity of some of the principal species of the cutaneous bacteria flora are directly controlled by neuropeptides released by sensory nerve endings including substance P and calcitonin gene-related peptide. Other factors involved in skin inflammation, such as atrial natriuretic peptides, vasoactive intestinal peptide, neuropeptide Y, and histamine should also directly and indirectly participate to the control of the cutaneous microbial flora. Herein, we highlight some of the more recent studies showing that the skin bacteria are interfering at multiple levels with cutaneous neurogenic inflammation. Understanding this mechanism was leading to the development of new cosmetic products, but this is also a promising route for novel therapeutic strategies for the care of cutaneous inflammatory diseases.