Magnaporthe oryzae is one of the most destructive fungal pathogen causing blast diseases in at least 50 grass species including wheat and rice. Although there has been comprehensive study on the fungicidal control of blast diseases, the development of pathogen resistance to commercially available products makes this approach inefficient. Novel strategies such as applying bioactive natural products against the blast fungus are required to control this economically important disease sustainably. Various classes of secondary metabolites including lipopeptides, macrolides, alkaloids, terpenoids, and phenolics from microorganisms and plants strongly suppress fungal growth and can also be effective in controlling blast diseases both in vitro and in vivo. However, precise control mechanisms of a specific blast fungus pathotype by antifungal secondary metabolites are still unclear. Commercial formulations of natural bioactive products should be cheap and safe, but the availability of these antifungal compounds for practical application is limited. This book chapter discusses the infection pathway of blast fungus and reviews naturally occurring antifungal secondary metabolites potential for controlling blast disease in cereal crops. The modes of actions of some potential antifungal secondary metabolites against blast fungus are also discussed.