Diseases caused by fungal and bacterial pathogens like Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae are responsible for considerable yield loss. Up to now, in rice, the modification of the expression of more than 60 genes from diverse origins has shown beneficial effects with respect to disease resistance. In this paper, we review this large set of data to identify the best genes and strategies to achieve disease resistance by transgenic approaches. Altered expression of genes involved in signal transduction and transcription may lead to many unwanted side effects, like lesion mimic phenotypes. Moreover, modification of resistance to abiotic stress has been neglected and should be carefully examined in the future. Genes like resistance genes and pathogenesis-related genes can confer broad spectrum and high levels of resistance to several pathogens. Preformed expression of defense is often observed but does not necessarily lead to detrimental effects. Although examples of gene pyramiding are scarce, they suggest that this is a very promising strategy. More field evaluation of the transgenic plants is required to draw final conclusions on the usefulness of these genes for improving disease resistance.