Modern antitumor therapy includes novel targeted and immunotherapeutic options specifically targeting tumor targets. However, many of these targets are also expressed in the constantly proliferating epidermis of the skin, leading to derangement of proliferation and differentiation of keratinocytes, inflammatory responses, skin barrier dysfunction, inhibition of antimicrobial peptides' synthesis, and toxic skin reactions. The article presents an overview of current data on microbiome disorders associated with toxic skin reactions. The potential mechanisms of skin microbiome changes inducing the occurrence and persistence of rashes during anticancer therapy are addressed.