Epidermolysis bullosa is a family of genetic disorders that cause blistering and shearing of the skin from even the mildest trauma. Care generally focuses on preventing infection, protecting the skin against trauma, attending to nutritional deficiencies and dietary complications, minimizing deformities and contractures, and providing psychological support for the entire family. One approach to the treatment of chronic wounds in Epidermolysis bullosa involves tissue engineering, where cells similar to those of the skin, grown on a three-dimensional scaffold, are used to induce healing. Charts of six young people (ages 8 years to 23 years; four girls, two boys) with recessive dystrophic Epidermolysis bullosa who received applications of a dermal skin substitute to persistent erosions at multiple body sites (55) at successive clinic visits were reviewed. Each patient received between seven and 32 skin substitute applications to between six and 19 sites; patients were followed for at least 8 weeks. At weeks 1 to 2, epidermal coverage ranged between 80% and 100%. Some sites had persistent coverage but others experienced breakdown. Four patients had hand surgery and the living skin substitute was used postsurgically to provide coverage for the epidermal defects. Overall in these six cases, the dermal skin substitute proved advantageous to wound protection, healing, and symptom relief. Compassionate care combined with optimal wound care and advancing technology may offer an effective antidote to the wounding and pain of this devastating disease.