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Fusarium species cause many diseases in plants and humans, which results in a great number of economic losses every year. The management of plant diseases and related human diseases caused by Fusarium is challenging as many kinds of Fusarium may be intrinsically resistant to antifungal drugs, not to mention the fact that they can acquire drug resistance, which is common in clinical practice. To date, the drug resistance of Fusarium is mainly related to target alterations, drug efflux and biofilm formation. This article reviews recent studies related to the mechanism of Fusarium resistance, and summarizes the key molecules affecting resistance.