Background: Lichens are symbiotic organisms with a fungal and an algal or a cyanobacterial partner. Lichens inhabit some of the harshest climates on earth and most lichen species are desiccation-tolerant. Lichen desiccation-tolerance has been studied at the biochemical level and through proteomics, but the underlying molecular genetic mechanisms remain largely unexplored. The objective of our study was to examine the effects of dehydration and rehydration on the gene expression of Cladonia rangiferina. Results: Samples of C. rangiferina were collected at several time points during both the dehydration and rehydration process and the gene expression intensities were measured using a custom DNA microarray. Several genes, which were differentially expressed in one or more time points, were identified. The microarray results were validated using qRT-PCR analysis. Enrichment analysis of differentially expressed transcripts was also performed to identify the Gene Ontology terms most associated with the rehydration and dehydration process. Conclusions: Our data identify differential expression patterns for hundreds of genes that are modulated during dehydration and rehydration in Cladonia rangiferina. These dehydration and rehydration events clearly differ from each other at the molecular level and the largest changes to gene expression are observed within minutes following rehydration. Distinct changes are observed during the earliest stage of rehydration and the mechanisms not appear to be shared with the later stages of wetting or with drying. Several of the most differentially expressed genes are similar to genes identified in previous studies that have investigated the molecular mechanisms of other desiccation-tolerant organisms. We present here the first microarray experiment for any lichen species and have for the first time studied the genetic mechanisms behind lichen desiccation-tolerance at the whole transcriptome level. Keywords: Lichen, Desiccation-tolerance, Gene expression, Microarray.