Wild-type adenovirus has high infectivity without dependence on target cell proliferation, but exhibit a potent cytopathic effect on the infected cells. Apoptosis is an active mode of cell death in which single cells are deleted in the midst of living tissues during development, organ maturation, and cell differentiation. However, bacterial toxicants and other pathogens including viruses can inappropriately activate the apoptotic program. Some early genes of adenoviruses including E1A, E1B and E3 have been reported to induce and /or inhibit the apoptosis in the infected cells. Current Ad vectors are E1A/E1B gene deleted, then theoretically non-replicative. However, Ad vectors also induce apoptosis in airway epithelial cells, suggesting that other Ad genes are involved in regulation of cell death. Recent evidences suggest that the accumulation of cells in G2/M transition may be associated with Ad vector-induced apoptosis in human airway epithelial cells. To minimize the induction of apoptosis of vector-infected cells is important for the prolongation of transduction efficiency of Ad vectors in designing human gene therapy.