Rice blast, caused by the fungus Magnaporthe oryzae, is the most devastating disease of rice which causes considerable economic loss worldwide. The interaction between rice and M. oryzae is an important model system for studying host-pathogen interactions. Since genomes of both species are sequenced, research is more focused by exploiting modern genetics, genomics, proteomics and bioinformatics. Recent research on functional genomics and candidate gene identification has helped to elucidate the role of resistance (R) and avirulence (Avr) genes and their interactions. Over the years, many avirulence genes (Avr) involved in pathogenicity and resistance genes (R) of rice involved in pathogen signaling molecules and defence response have been identified and characterized. Recent development in cloning of Avr genes (13) and R genes (22) and identification of many quantitative trait loci (QTL) has improved our understanding of rice-M. oryzae interaction at molecular level. This chapter is focusses on the current R and Avr genes cloned and characterized their structure, function and co-evolution, and the future research directions to study and understand the molecular mechanism of rice-M. oryzae interactions for better targeting and exploitation of host plant resistance towards management of this disease.