The NPRI (nonexpressor of pathogenesis-related genes (1) gene, firstly cloned in Arabidopsis thaliana, is a key gene involved in regulation of plant disease resistance. It plays a pivotal role not only in systemic acquired resistance (SAR) and induced systemic resistance (ISR), but also in basic resistance and resistance (R) gene-dependent resistance. NPR1 monomerization induced by enhanced reducing condition after oxidative burst, and the accumulation of NPR1 monomers in the nuclei, are required and enough for expression of PR (pathogenesis-related) genes and SAR. NPR1 regulates PR gene expression through interaction with TGA transcription factors (TF). As a cross-talk point of a variety of defense signaling pathways, probably through direct or indirect interacting with some WRKY TFs and a NPR1-like protein NPR4, NPR1 is essential in balancing salicylic acid- and jasmonic acid- dependent signal transduction pathways, which is achieved through an unknown mechanism in the cytosol. The possible application of NPR1 in plant protection is also discussed in this review.