We review progress in research on antifungal proteins and other mechanisms that provide the biochemical basis for host plant resistance to stalk rot and grain molds. Stalk rot, caused by Fusarium spp., leads to substantial yield loss due to poor grain filling and/or lodging. Transgenic sorghum plants that express high levels of chitinase have less stalk rot when exposed to conidia of Fusarium thapsinum. Grain mold of sorghum is associated with warm humid environments and results from colonization of the caryopsis by several fungi, e.g., F thapsinum, Curvularia lunata, and Alternaria alternata. Biochemical mechanisms that may contribute to grain mold resistance include tannins, phenolic compounds, red pericarp, hard endosperm, and antifungal proteins. The effects attributed to these characters appear to be additive, and pyramiding of genes is a feasible approach to limit grain deterioration.