Epidermolysis bullosa (EB) is a group of hereditary skin diseases, or genodermatoses, characterized by the formation of severe, chronic blisters with painful and life-threatening complications. Despite the previous and ongoing progress in the field, there are still no effective causative treatments for EB. The treatment is limited to relieving symptoms, which—depending on disease severity—may involve skin (blisters, poorly healing wounds caused by the slightest mechanical stimuli, contractures, scarring, pseudosyndactyly) and internal organ abnormalities (esophageal, pyloric, or duodenal atresia; renal failure; and hematopoietic abnormalities). The last decade saw a series of important discoveries that paved the way for new treatment methods, including gene therapy, bone marrow transplantation, cell therapy (allogenic fibroblasts, mesenchymal stem cells [MSCs], and clinical use of induced pluripotent stem cells. Tissue engineering experts are attempting to develop skin-like structures that can facilitate the process of healing to promote skin reconstruction in injuries that are currently incurable. However, this is incredibly challenging, due to the complex structure and the many functions of the skin. Below, we characterize EB and present its potential treatment methods. Despite the cure for EB being still out of reach, recent data from animal models and initial clinical trials in humans have raised patients’, clinicians’, and researchers’ expectations. Consequently, modifying the course of the disease and improving the quality of life have become possible. Moreover, the conclusions drawn based on EB treatment may considerably improve the treatment of other genetic diseases.