Pulmonary fibrosis is characterized by epithelial injury, abnormal tissue repair, fibroproliferation and loss of pulmonary function as a result of a complex interaction of multiple cellular and molecular processes. There is accumulating evidence in support of a role for apoptosis in the pathogenesis of interstitial lung diseases. The Bcl-2 (B-cell lymphoma-2) family of proteins, which consists of antiapoptotic and pro-apoptotic members, is a critical regulator for apoptosis and development of pulmonary fibrosis. The association between Bcl-2 family members and various pathways and mediators has been also described in the pulmonary fibrosis. This article reviews the recent advances regarding the roles of Bcl-2 family as the apoptosis-regulatory factors in pulmonary fibrosis from human tissue studies, animal models, ex vivo and in vitro studies. Further understanding of apoptosis signaling regulation through Bcl-2 family proteins in the lung tissue may lead to better design of new therapeutic interventions for pulmonary fibrosis.