In all forms of epidermolysis bullosa (EB), skin fragility may result in bacterial colonization or infection, particularly in the more severe forms where wounds may be multiple and long-standing. A balance exists between a wound’s bacterial load and the host defenses, such that there is a spectrum from simple contamination, through colonization, critical colonization, to overt infection. The increased bioburden in critically colonized or infected wounds impairs healing and therefore recognition of these situations, and appropriate measures to promote a healing environment, are fundamental to the care of EB wounds.