Pharmacological studies on flavonoids have always drawn much interest for many years. Icaritin (ICT), a representative flavone containing an 8-prenyl group, is a principal compound detected in medicinal plants of the genus Epimedum, the family Berberidaceae. Experimental results in the phytochemistry and pharmacology of this molecule are abundant now, but a deep overview has not been carried out. The goal of this review is to provide an insight into the natural observation, biosynthesis, biotransformation, synthesis, pharmacology, and pharmacokinetics of prenyl flavone ICT. The relevant data on ICT was collected from bibliographic sources, like Google Scholar, Web of Science, Sci-Finder, and various published journals. “Icaritin” alone or in combination is the main keyword to seek for references, and references have been updated till now. ICT is among the characteristic phytomolecules of Epimedum plants. Bacteria monitored its biosynthesis and biotransformation, while this agent was rapidly synthesized from phloroglucinol by microwave-assistance Claisen rearrangement. ICT is a potential agent in numerous in vitro and in vivo pharmacological records, which demonstrated its role in cancer treatments via apoptotic-related mechanisms. It also brings in various health benefits since it reduced harmful effects on the liver, lung, heart, bone, blood, and skin, and improved immune responses. Pharmacokinetic outcomes indicated that its metabolic pathway involved hydration, hydroxylation, dehydrogenation, glycosylation, and glucuronidation. Molecule mechanisms of action at a cellular level are predominant, but clinical studies are expected to get more. Structure-activity relationship records seem insufficient, and the studies on nano-combined approaches to improve its soluble property in living bodied medium are needed.