Regulation and execution of epidermal terminal differentiation, apoptosis and cellular senescence share some molecular and cellular features. The three phenomena result in suppression of proliferation and in some instances they seem to overlap. The boundaries between keratinocyte terminal differentiation and senescence are unclear and the former has been proposed to be a form of apoptosis. However, cumulative evidence argues that they are alternative, independent responses to different stimuli. I summarize in this review classical and recent evidence underlying the molecular control of these biological processes and propose a rationale to understand their nature and function in epidermis. (C) 2000 Elsevier Science Inc. All rights reserved.