and Aim: Increasing prevalence of nosocomial infections, due to arbitrary use of antibiotics, has caused serious health problems. Natural compounds have been used for many years for the treatment of many infections. Rare actinobacteria are one of the main sources used for discovery and isolation of natural compounds with pharmaceutical properties. The main purpose of this review article was to study new metabolites derived from rare actinobacteria, and evaluate their medicinal and

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... applications. Materials and Methods: This study included over 183 peer-reviewed papers from the databases of Scopus, PubMed, Web of Science and ScienceDirect from 2015 to 2021. Results: In this study chemical structure and biological activity of 113 new compounds isolated from rare actinobacteria were evaluated. This study also showed that rare actinobacteria have the capability to produce a variety of compounds such as alkaloids, flavonoids, terpenes and polyketides with a diverse range of biological activities including antibacterial, antifungal, antiviral and anticancer properties. Conclusion: The results of this study revealed that rare actinobacteria can be considered as an excellent source for the production of natural active compounds with high potentials for therapeutic and applied medical, pharmaceutical and agricultural biotechnology. It also showed the key role of these compounds in the development of necessary drugs for humans in the near future