Mycotoxins are secondary metabolites produced by fungi. Food/feed contamination by mycotoxins is a great threat to food safety. The contamination can occur along the food chain and can cause many diseases in humans and animals, and it also can cause economic losses. Many detoxification methods, including physical, chemical, and biological techniques, have been established to eliminate mycotoxins in food/feed. The biological method, with mycotoxin detoxification by microorganisms, is reliable, efficient, less costly, and easy to use compared with physical and chemical ones. However, it is important to discover the metabolite's toxicity resulting from mycotoxin biodegradation. These compounds can be less or more toxic than the parent. On the other hand, mechanisms involved in a mycotoxin's biological control remain still unclear. Mostly, there is little information about the method used by microorganisms to control mycotoxins. Therefore, this article presents an overview of the most toxic mycotoxins and the different microorganisms that have a mycotoxin detoxification ability. At the same time, different screening methods for degradation compound elucidation are given. In addition, the review summarizes mechanisms of mycotoxin biodegradation and gives some applications.