Pleural and pulmonary fibrosis (asbestosis) are ramifications of occupational exposures to asbestos fibers, a diverse family of ubiquitous, naturally-occurring minerals. The pathogenesis of asbestos-associated fibrosis involves the participation of a number of cell types and is characterized by an early and persistent inflammatory response that involves the generation of oxidants, growth factors, chemokines, and cytokines. These mediators may also contribute directly to cell injury, proliferation, and fibrogenesis. After interaction with cells, asbestos fibers trigger a number of signaling cascades involving mitogen-activated protein kinases (MAPK) and nuclear factor kappa-B (NF-kappaB). Activation of transcription factors such as NF-kappaB and activator protein-1 (AP-1) may be linked to increases in early response genes (e.g., c-jun and c-fos) which govern proliferation, apoptosis, and inflammatory changes in the cells of the lung. The goal of this article is to review the cellular and molecular mechanisms of asbestos-induced fibrosis that may be critical to the development of effective treatment regimens.