Salicylic acid (SA) and the NIM1/NPR1 protein have both been demonstrated to be required for systemic acquired resistance (SAR) and implicated in expression of race-specific resistance. In this work, we analyzed the role that each of these molecules play in the resistance response triggered by members of two subclasses of resistance (R) genes, members of which recognize unrelated pathogens. We tested the ability of TIR and coiled-coil-class (also known as leucine-zipper-class) R genes to confer resistance to Pseudomonas syringae pv. tomato or Peronospora parasitica in SA-depleted (NahG) and nim1/npr1 plants. We found that all of the P. syringae pv. tomato-specific R genes tested were dependent upon SA accumulation, while none showed strong dependence upon NIM1/NPR1 activity. A similar SA dependence was observed for the P. parasitica TIR and CC-class R genes RPP5 and RPP8, respectively. However, the P. parasitica-specific R genes differed in their requirement for NIM1/NPR1, with just RPP5 depending upon NIM1/NPR1 activity for effectiveness. These data are consistent with the hypothesis that at least in Arabidopsis, SA accumulation is necessary for the majority of R-gene-triggered resistance, while the role of NIM1/NPR in race-specific resistance is limited to resistance to P. parasitica mediated by TIR-class R genes.