In the past years, our view of the molecular and cellular mechanisms that ensure the self-renewal of the skin has dramatically changed. Several populations of stem cells have been identified that differ in their spatio-temporal contribution to their compartment in steady-state and damaged conditions, suggesting that epidermal stem cell heterogeneity is far greater than previously anticipated. There is also increasing evidence that these different stem cells require a tightly controlled spatial and temporal communication between other skin residents to carry out their function.