Considerable progress has been made in mice toward identifying the signals that regulate lung epithelial stem cell self-renewal and differentiation. These include Notch, Hippo/Yap, ROS/Nrf2, EGF, FGF, c-myb, and cytokines including IL-4, -13 and -6. Neighboring epithelial cells, stromal cells (including mesenchymal cells, fibroblasts, smooth muscle cells, and endothelium) and immune cells all represent potential sources for these factors. Distinct stem cell niches have been defined in adult mouse trachea and lung in the steady state and there is increasing evidence that in different pathological conditions stem cell niches are affected and altered.