We present clinical experience with 110 reconstructive procedures in 25 patients with epidermolysis bullosa, a group of rare heritable disorders characterized by marked fragility of the skin and mucosa. We discuss management of hand and foot deformities unique to epidermolysis bullosa patients, excision of squamous cell carcinoma, and reconstruction of oral, nasal, and ocular tissues. All patients underwent these procedures without major surgical or anesthetic complications. We analyze surgical outcome and formulate guidelines to avoid damaging the skin and mucosa.