Overexpression (OE) was used to study the role of the Arabidopsis Golden2-like (GLK1) transcriptional activator in regulating gene expression. Affymetrix Gene Chip and RT-PCR analyses indicated that GLK1 OE in Arabidopsis reprogrammed gene expression networks to enhance a high constitutive expression of genes encoding disease defense related proteins. These include PR10, isochorismate synthase, antimicrobial peptides, glycosyl hydrolases, MATE efflux and other genes associated with pathogen response and detoxification. However, PR1, an indicator of systemic acquired resistance (SAR), was downregulated in GLK1 OE. GLK1 OE in Arabidopsis confers resistance to Fusarium graminearum, a broad host pathogen responsible for major losses in cereal crops. This is the first identification of the GLK1 'regulon' and a novel role for GLK1 in plant defense, suggesting its potential use for providing disease resistance in crop plants.