Cultures of human epidermal keratinocytes retain many of the characteristics of the tissue from which they are derived, and are therefore useful as an experimental model for studying stem cell properties. The cultures provide evidence that the mechanisms regulating keratinocyte proliferation are complex. The dividing cell compartment is heterogeneous, containing some cells with stem cell characteristics and others that may correspond to transit amplifying cells. The overall growth rate of the cultures is influenced by a wide range of growth stimulatory and inhibitory molecules, but it is not clear whether responsiveness to these factors differs between the different subpopulations of dividing cells. Furthermore, keratinocytes are able to express molecules that regulate their own growth. The cultures are able to achieve at least a partial homeostatic balance between proliferation and terminal differentiation and can regenerate the suprabasal cell layers following injury. Finally, a range of new experimental approaches hold promise for future studies of how keratinocyte proliferation and terminal differentiation are controlled.