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Epimedium has been widely used in traditional Chinese medicine for several thousands of years. This plant is known for tonifying kidney Yang, strengthening muscles and bones, and dispelling wind and dampness. It is worth noting that icaritin, a prenylated flavonoid isolated from Epimedium, has received increasing attention in recent years due to its wide range of pharmacological activities. Icaritin exhibits significant therapeutic potential against various diseases, such as osteoporosis, tumors (hepatocellular carcinoma, stomach cancer, breast cancer, and glioblastoma), cerebral ischemia skin injury, thrombocytopenia, and systemic lupus erythematosus. We review the pharmacological activities of icaritin and its potential molecular mechanisms for the treatment of related diseases. The data suggest that icaritin can have the pharmacological effects of mediating Wnt/ β -catenin, IL-6/JAK2/STAT3, AMPK/mTOR, PTEN/AKT, MAPK, NF- κ B, and other signaling pathways. This paper also discusses the progress of clinical trials of icaritin. Icaritin was approved by the State Food and Drug Administration in January 2022 for the treatment of advanced HCC, and has various clinical drug prospects. Although it has some disadvantages, including poor solubility, and low bioavailability, icaritin is still a prospective candidate for the development of naturally derived drugs, especially in the treatment of tumors and inflammatory diseases. This review aims to update and deepen the understanding of icaritin, and provide a theoretical basis for its further study. [ABSTRACT FROM AUTHOR]