Molds pose a severe challenge to agriculture because they cause very large crop losses. For this reason, synthetic fungicides have been used for a long time. Without adequate protection against pests and various pathogens, crop losses could be as high as 30–40%. However, concerns mainly about the environmental impact of synthetic antifungals and human health risk have prompted a search for natural alternatives. But do natural remedies only have advantages? This article reviews the current state of knowledge on the use of antifungal substances in agriculture to protect seeds against phytopathogens. The advantages and disadvantages of using both synthetic and natural fungicides to protect cereal grains were discussed, indicating specific examples and mechanisms of action. The possibilities of an integrated control approach, combining cultural, biological, and chemical methods are described, constituting a holistic strategy for sustainable mold management in the grain industry.