Plants and animals maintain evolutionarily conserved innate immune systems that give rise to durable resistances. Systemic acquired resistance (SAR) confers plant-wide immunity towards a broad spectrum of pathogens. Numerous studies have revealed that NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR) is a key regulator of SAR. Here, we review the mechanisms of NPR1 action in concert with its paralogues NPR3 and NPR4 and other SAR players. We provide insights into the mechanisms of salicylic acid (SA) perception. We discuss the binding of NPR3 and NPR4 with SA that modulates NPR1 coactivator capacity, leading to diverse immune outputs. Finally, we highlight the function of NPR1 as a bona fide SA receptor and propose a possible model of SA perception in planta. © 2013 .