The global consumption of both fresh apples and apple-based products is high in accordance with the increasing population demand. However, invasion of fruit surfaces or wounds by Penicillium expansum causing blue mold and possible production of patulin is common occurrence. Patulin, a secondary metabolite of Penicillium spp., has been a serious global health and economic problem without a realistic solution. An in-depth knowledge of factors influencing patulin accumulation and challenges with its presence in apple fruit can contribute significantly to the search for sustainable control measures. In this chapter, the distribution and economic implications of patulin, toxicity, and its occurrence in apple fruit and its derived products have been discussed. Also, the effect of fungicides on decay fungi and patulin production, control of patulin by antagonistic yeasts and other amendment treatments, and finally the degradation mechanisms have been thoroughly discussed. From literature, the most important mechanisms of biodegradation or removal of patulin include the microbial cells biosorption of patulin, microbial enzyme degradation of patulin and patulin–glutathione adducts, or patulin reactions with thiol group existing in protein extracts. Lastly, the presence of patulin in growth media induces the synthesis of degrading enzymes in patulin-resistant/degrading yeasts.