NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) is a master regulator of salicylic acid (SA)-mediated systemic acquired resistance (SAR), a broad-spectrum disease resistance mechanism in plants. NPR1 controls approximately 90% of SA-dependent transcriptome in Arabidopsis. Here, we discuss how pathogen effectors manipulate NPR1 functions in different cellular compartments to establish disease.