Asbestos products had been widely used until 2007 in Korea since the 1930s. A total ban on their production and applications has been imposed because of the toxic effect of asbestos fibers on the human health. The inhaled asbestos fibers increase reactive oxygen species and inflammatory reactions in the respiratory airway including the alveolar sac, resulting in DNA damages and secretion of several inflammatory cytokines or chemokines. These paracrine communications promote the proliferation of fibroblasts and the synthesis of collagen fibers, thereby depositing them into the extracellular matrix at the interstitial space of alveoli. The fibrotic tissue hindered the gas exchange in the alveolus. This reviews describes not only the cytotoxic effects of asbestos fibers with different physical or chemical characteristics but also the interaction of cells that make up the respiratory airway to understand the molecular or cellular mechanisms of asbestos fiber-induced toxicity. In addition, we propose a pulmonary toxicity research technique based on the mini-lung that can mimic human respiratory system as an alternative to overcome the limitations of the conventional risk assessment of asbestos fibers.