Diseases are a potential threat to global food security but plants have evolved an extensive array of methodologies to cope with the invading pathogens. Non-host resistance and quantitative resistance are broad spectrum forms of resistance, and all kinds of resistances are controlled by extremely diverse genes called "R-genes". R-genes follow different mechanisms to defend plants and PAMP-induced defenses in susceptible host plants are referred to as basal resistance. Genetic and phenotypic diversity are vital in maize (Zea mays L.); as such, genome wide association study (GWAS) along with certain other methodologies can explore the maximum means of genetic diversity. Exploring the complete genetic architecture to manipulate maize genetically reduces the losses from hazardous diseases. Genomic studies can reveal the interaction between different genes and their pathways. By confirming the specific role of these genes and protein-protein interaction (proteomics) via advanced molecular and bioinformatics tools, we can shed a light on the most complicated and abstruse phenomena of resistance. © 2012 Institute of Botany, Chinese Academy of Sciences.