The increasing use of plant-based ingredients as a replacement for fishmeal poses the high risk of introducing mycotoxins into aquafeed. However, appropriate low-dose supplementation demonstrates how aquatic animals can cope with “anti-nutritional” factors within their adaptive response, indicating that even these compounds may have some nutritional value. In addition, knowledge of the underlying mechanisms of the adaptive response may provide physiological, transcriptomic, and epigenetic means to more sustainably utilize even this “worthless” food source. Several strategies have been used and are being discussed to reduce mycotoxin contamination in aquaculture practice: co-feeding of adsorbents, antioxidants and other chemicals, phytobiotics, prebiotics, or probiotics. The use of antisense non-coding RNAs has not yet been tested but appears promising.