Rice diseases (bacterial, fungal, or viral) threaten food productivity. Host resistance is the most efficient, environmentally friendly method to cope with such diverse pathogens. Quantitative resistance conferred by quantitative trait loci (QTLs) is a valuable resource for rice disease resistance improvement. Although QTLs confer partial but durable resistance to many pathogen species in different crop plants, the molecular mechanisms of quantitative disease resistance remain mostly unknown. Quantitative resistance and non-host resistance are types of broad-spectrum resistance, which are mediated by resistance (R) genes. Because R genes activate different resistance pathways, investigating the genetic spectrum of resistance may lead to minimal losses from harmful diseases. Genome studies can reveal interactions between different genes and their pathways and provide insight into gene functions. Protein–protein interaction (proteomics) studies using molecular and bioinformatics tools may further enlighten our understanding of resistance phenomena.