The concept of the exposome, formulated more than fifteen years ago, is increasingly discussed in the modern scientific literature. The term “exposome” is understood as a cumulative measure of the impact of environmental factors on an individual throughout his or her life (from the prenatal period to death) and the biological response associated with it. The sum of these factors has a significant impact on the occurrence, course, and treatment efficacy of multifactorial diseases. The skin is a border organ and is constantly exposed to environmental influences, i.e., it is a target for the exposome. The influence of the latter components has been described in skin aging, atopic dermatitis, and malignant skin neoplasms. Acne is one of the most common chronic inflammatory dermatoses. Over the past decade, the worldwide increase in the incidence of acne, its early onset and a prolonged course, affecting adult men and women, has been noted. The review presents an analysis of the data on the effects of the components of the exposome – diet, medications, stress, and pollutants-on the course of acne. Particular attention is paid to the few data on the nature of interaction between the components of the exposome and the skin microbiome, which, on the one hand, is involved in the pathogenesis of dermatoses, including acne, and, on the other hand, is changed under the influence of exposome factors, acting as an intermediary between the environment and the human body. The search for environmental factors has at least two objectives: the discovery of potential pathogenetic links, the strength of their relationship with the clinical manifestations of the disease to develop new therapies aimed at new targets; and the creation and recommendation of a protective regime for factors with a proven effect on the course of the disease, for patients suffering from acne.