This review focuses on recent evidences about human microbiome composition and functions, exploring the potential implication of its impairment in some diffuse and invalidating inflammatory skin diseases, such as atopic dermatitis, psoriasis, hidradenitis suppurativa and acne. We analysed current scientific literature, focusing on the current evidences about gut and skin microbiome composition and the complex dialogue between microbes and the host. Finally, we examined the consequences of this dialogue for health and skin diseases. This review highlights how human microbes interact with different anatomic niches modifying the state of immune activation, skin barrier status, microbe-host and microbe-microbe interactions. It also shows as most of the factors affecting gut and skin microorganisms' activity have demonstrated to be effective also in modulating chronic inflammatory skin diseases. More and more evidences demonstrate that human microbiome plays a key role in human health and diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.