This chapter provides a detailed description of the development and use of in vitro and in vivo experimental models of asbestos-related diseases. Decades of experimental studies have led to better understanding of the toxicity and health risks of asbestos exposure as well as mechanistic insights into pathological processes induced by asbestos. We examine mechanisms of fiber deposition and clearance and critical role of fiber dimensions. We describe models of in vitro asbestos exposure as well several in vivo models of exposure through various routes, including inhalation in rodents. Moreover, these models have been used to explore cell and molecular mechanisms of asbestos-induced fibrogenesis and carcinogenesis. This includes discovered roles of structural and immune cells, cytotoxicity, oxidants, critical signaling pathways, tumor suppressor and oncogenes, as well as the impact of fiber size. Understanding these mechanisms is crucial for reducing health risks and improving development of new therapies for asbestos-related disease.