Ankylosing spondylitis (AS) is the prototypic and most prevalent and debilitating spondyloarthropathy, a group of arthritides where the spine and pelvis are specifically targeted. Unlike many other forms of arthritis in which joint damage is mediated through tissue destruction, in AS uncontrolled bone formation occurs, frequently resulting in joint fusion and consequently significant disability. It is estimated that there are 2.4 million spondyloarthritis sufferers in the U.S., twice as many as rheumatoid arthritis. The pathogenesis of AS is very poorly understood and both genetics and gene expression profiling approaches have been utilized to elucidate the underlying mechanisms and pathways that drive the disease. Using powerful genome-wide association study approaches a number of candidate genes have been found to be associated with AS. However, although such approaches can identify genes that can contribute to the disease process, they do not inform us of the actual changes in gene/cell activity at any point in the disease process. Expression profiling allows us to take a "snapshot" of cellular activity and what gene activity changes are underlying those changes. A number of expression profiling studies have been undertaken in AS, looking at both circulating cells and tissues from affected joints. The results to date have been somewhat disappointing with little consensus on gene activity changes due to the low power of the studies undertaken. Some more recent better powered studies have identified diagnostic expression profiles that do point to a possible role for expression profiling in early AS diagnosis. Future studies will require collaborative approaches to target specific disease stages and sites with larger numbers of samples.