Uterine leiomyomata (fibroids) are a leading women's health problem, resulting in significant morbidity and surgical intervention. As benign clonal tumors, leiomyomata also represent a target well suited to molecular analysis. Familial studies and genetic syndromes featuring leiomyomata provide compelling evidence that genetic alterations may cause fibroid development, but the specific genes involved in leiomyoma development have not been identified. Microarrays permit simultaneous comparison of the relative expression of thousands of genes, thereby highlighting specific genes that may play a role in the development of leiomyomata. Microarray studies conducted by several laboratories have identified candidate genes. However, few gene products have been confirmed with alternative experimental approaches. The objective of this article is to focus on the insights provided by microarray studies investigating leiomyoma development. Such studies suggest that although hormonal control of leiomyoma growth is observed, there are other critical pathways involved in development of the leiomyoma cell phenotype that warrant investigation. In particular, expression of extracellular matrix genes in leiomyomata is deranged and such genes represent potential novel targets for therapy.