Mesothelioma is an asbestos-related neoplasm of the thoracic pleura about which little is known and for which effective therapy is lacking. Large-scale transcriptional profiling using microarrays is frequently a part of studies to explore gene expression patterns in cancer and other diseases. In general, microarray based experiments can facilitate the identification of tumor molecular markers, provide clues relating to mechanisms carcinogenesis, as well as aid in the discovery of candidate targets for therapy. Relatively few studies of this sort have been attempted for mesothelioma, likely due to its relatively rare incidence and by extension the difficulty in acquiring suitable tissues for analysis. Microarray analysis of mesothelioma will likely lead to a better understanding of a highly lethal malignancy and result in the identification of potential therapeutic targets to ultimately affect better treatment options and patient clinical outcome. This mini-review will address general issues pertaining to all expression profiling experiments (e.g., data interpretation) and summarize similar studies that have been attempted for mesothelioma.