Technical Abstract: Recent genomic analyses of arthropod defense mechanisms suggest conservation of key elements underlying responses to pathogens, parasites, and stresses. At the center of pathogen-induced immune response are signaling pathways triggered by the recognition of fungal, bacterial, and viral signatures. These pathways result in the production of response molecules, such as antimicrobial peptides and lysozymes, which degrade or destroy invaders. The purpose of this study was to characterize the immune and stress gene repertoire of the pea aphid (Acyrthosiphon pisum), a distant relative of previously characterized insects. Strikingly, pea aphids appear to be missing genes thought critical for recognition, signaling, and microbial degradation in insects. In line with results of gene annotation, experimental analyses designed to characterize immune response through the isolation of RNA transcripts and proteins from immune-challenged pea aphids uncovered few immune-related products. Gene expression studies, however, indicated some differential expression of immune and stress-related genes upon challenge. The absence of genes thought critical to the insect immune response in the pea aphid suggests that the traditional view of insect immunity may not be as broadly applicable as once thought. The limitations of the aphid immune system may be representative of a broad range of insects, or may be aphid specific. We suggest that several aspects of the aphid life style could facilitate survival without strong immune protection.