<sec><title>Background</title><p>Plants defend themselves against herbivorous insects, utilizing both constitutive and inducible defenses. Induced defenses are controlled by several phytohormone-mediated signaling pathways. Here, we analyze transcriptional changes in the North American Arabidopsis relative <italic>Boechera divaricarpa</italic> in response to larval herbivory by the crucifer specialist lepidopteran <italic>Plutella xylostella</italic> (diamondback moth) and by the generalist lepidopteran <italic>Trichoplusia ni</italic> (cabbage semilooper), and compare them to wounding and exogenous phytohormone application.</p></sec><sec><title>Methodology/Principal Findings</title><p>We use a custom macroarray constructed from <italic>B. divaricarpa</italic> herbivory-regulated cDNAs identified by suppression subtractive hybridization and from known stress-responsive <italic>A. thaliana</italic> genes for transcript profiling after insect herbivory, wounding and in response to jasmonate, salicylate and ethylene. In addition, we introduce path analysis as a novel approach to analyze transcript profiles. Path analyses reveal that transcriptional responses to the crucifer specialist <italic>P. xylostella</italic> are primarily determined by direct effects of the ethylene and salicylate pathways, whereas responses to the generalist <italic>T. ni</italic> are influenced by the ethylene and jasmonate pathways. Wound-induced transcriptional changes are influenced by all three pathways, with jasmonate having the strongest effect.</p></sec><sec><title>Conclusions/Significance</title><p>Our results show that insect herbivory is distinct from simple mechanical plant damage, and that different lepidopteran herbivores elicit different transcriptional responses.</p></sec>