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Ethnopharmacological Relevance: Usnea sp. is a fruticose thalli lichen with interesting medicinal properties. Since ancient times, Usnea sp. has been used in traditional medicine worldwide to treat various diseases. The broad scientific studies on this lichen have proved its multidirectional biological effect, such as antimicrobial activity, which is attributed to its usnic acid content., Purpose: The main aim of this review is to provide an up-to-date overview of the antimicrobial activities of Usnea sp., including the traditional and medicinal uses, and a critical evaluation of the presented data. Also, the mechanism of this type of action will be explained., Methods: To prepare this manuscript, the information was extracted from scientific databases (Pubmed, ScienceDirect, Wiley, Springer, and Google Scholar), books, and theses. The available scientific information was critically analysed., Results: Analysis of the scientific literature regarding traditional uses and bioactivity research showed that Usnea sp. extracts exhibit high antibacterial activity. The Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, and Mycobacterium tuberculosis) and aquatic oomycetous fungi were the most sensitive Usnea sp. extracts. Moderate activity against Malassezia furfur and dermatophytes was observed, as well. Gram-negative bacteria, yeast, and fungi were more frequently resistant to Usnea sp. extracts (included Escherichia coli, Candida sp., Saccharomyces cerevisiae, and Aspergillus sp.). The antiviral activity of Usnea sp. was limited., Conclusion: The results show that the use of Usnea sp. in traditional medicine can be scientifically documented. Studies show that usnic acid is the active compound present in Usnea sp. extracts. This compound, which has a high antibacterial and cytotoxic activity, exists in large quantities in low-polarity extracts, and low concentration in these of high-polarity. Usnea sp. extracts contain compounds other than usnic acid as well with biological effects. Usnea barbata is a species that has been employed in modern-day cosmetic and pharmaceutical preparations. The information presented in the review can be considered as a source of knowledge about the Usnea sp. It presents research on biological properties reported for different species of Usnea genus and thus can facilitate their use in medicine., (Copyright © 2020 Elsevier B.V. All rights reserved.)