We describe for the first time functional clusters of genes that are modulated during the differentiation of osteoclasts. Pathway analysis was applied to gene array data generated from affymetrix chips hybridized to RNA isolated from RAW264.7 cells exposed to RANK-ligand (RANK-L) for 5 days. This analysis revealed major functional gene clusters that were either up- or down-regulated during osteoclastogenesis. Some of the genes within the clusters have known functions, while others do not. We discuss herein the relevance of these functional gene clusters and their modulation to biological processes underlying the formation, function, and fate of osteoclasts. (C) 2007 Elsevier Inc. All rights reserved.