Gene expression studies represent a new and challenging approach that allows molecular dissection of complex diseases such as rheumatoid arthritis (RA). Optimally, gene analysis should be conducted in isolated populations of cells so that the differential gene expression may be directly correlated with transcription of genes. RA fibroblasts constitute the majority of the expanding synovial cell mass in the RA joint, and alterations in their phenotype are likely to be important in the pathogenic process. However, RA involves many cell types from tissues adjacent to the synovium and the important cell types are not known. Analysis of gene expression profiles by processing a complex tissue such as whole paws can provide useful information about dysregulated genes, not only in the synoviocytes but also in other, neighbouring cells (monocytes, osteocytes and chondrocytes) that may contribute to disease pathology. This review will focus on the use of gene expression studies, both in isolated cells and in whole tissue, as a means of studying the molecular mechanisms involved particularly in the angiogenic process in RA. In particular, we will focus on synovial angiogenesis, since the synovial vascular density is altered in RA. This will provide an increased surface area for inflammatory cell trafficking, as well as delivering nutrients and oxygen to the proliferating synovial cells. Therapeutic approaches targeting angiogenic factors such as vascular endothelial growth factor (VEGF), which is increased in RA, have already shown some clinical success in oncology, and in mouse models of arthritis.