Wheat production is constantly threatened by many kinds of diseases, such as Fusarium head blight (FHB), rusts, powdery mildew, leaf blotch, wheat blast etc. Wheat plants deploy different defense mechanisms and appropriate immune responses to defend them against these pathogens. In model plants, such as Arabidopsis and rice, the pathogen infection activates plant immune responses either through Pathogen/Microbe Associated Molecular Pattern (P/MAMP) Triggered Immunity (PTI) and Effector Triggered Immunity (ETI) pathways. However, the molecular pathways associated to wheat disease resistance are poorly understood. We recently cloned several wheat disease resistance genes (R genes), Pm5e, Pm24, Pm41, MlWE18, MlIW172, Yr30/Lr27, Lr13/Ne2, and Sb3, conferring resistance to powdery mildew (Blumeria graminis f. sp. tritici), stripe rust (Puccinia striiformis f. sp. tritici), leaf rust (P. triticina), and spot blotch (Bipolaris sorokiniana). These genes encoded nucleotide-binding and leucine-rich repeat receptor (NLR), wheat tandem kinase (WTK), and transmembrane proteins. The avirulence (Avr) genes AvrPm5e and AvrPm41, also known as effectors, were also isolated to characterize their gene-for-gene interactions with the corresponding NLRs. We further re-constructed the molecular pathways of those genes and identified key proteins that interact with the R genes. We found crosstalk between PTI, ETI and Effector Triggered Susceptibility (ETS) pathways contributed wheat immunity conferring biotrophic and necrotrophic pathogens infections. The understanding of genetic and genomic nature of wheat disease resistance genes, corresponding Avr effectors and the key members involved in the host-pathogen interaction pathways will shed light on molecular designing novel wheat cultivars with broad spectrum and durable disease resistance.