Understanding the host response to Uromyces sp., the causal agent of rust in many crop species, is crucial in elucidating the specific biology of rust resistance. In an attempt to unravel the Medicago truncatula-U. striatus interaction, we performed a global analysis of transcription factor (TF) expression in resistant and susceptible accessions of the model plant M. truncatula during infection with U. striatus. For this purpose, an established qPCR platform was applied, consisting of specific primer pairs for more than 1,000 predicted TF genes. A total of 107 putative TF genes out of the 1,084 studied were differentially expressed. Thirteen of the TFs that were differentially expressed between resistant and susceptible genotypes are known to be relevant in cellular defense. These data suggest that resistance could be mediated both by genes that are constitutively expressed and by genes, which are activated/repressed when plants are inoculated. These defense related TFs sequences were amplified in chickpea DNA with the aim of determining the location of these genes on the genetic map of this crop and identifying possible DNA regions involved in resistance mechanisms.