The light environment is a key factor that governs a multitude of developmental processes during the entire life cycle of plants. An important and increasing part of the incident sunlight encompasses a segment of the UV-B region (280–320 nm) that is not entirely absorbed by the ozone layer in the stratosphere of the earth. This portion of the solar radiation, which inevitably reaches the sessile plants, can act both as an environmental stress factor and an informational signal. To identify Arabidopsis genes involved in the UV response, we monitored the gene expression profile of UV-B-irradiated seedlings by using high-density oligonucleotide microarrays comprising almost the full Arabidopsis genome (>24,000 genes). A robust set of early low-level UV-B-responsive genes, 100 activated and 7 repressed, was identified. In all cases analyzed, UV-B induction was found to be independent of known photoreceptors. This group of genes is suggested to represent the molecular readout of the signaling cascade triggered by the elusive UV-B photoreceptor(s). Moreover, our analysis identified interactions between cellular responses to different UV-B ranges that led us to postulate the presence of partially distinct but interacting UV-B perception and signaling mechanisms. Finally, we demonstrate that the bZIP transcription factor HY5 is required for UV-B-mediated regulation of a subset of genes.