Xeroderma pigmentosum (XP) is a rare genodermatosis transmitted as an autosomal and recessive trait. XP patients are highly photosensitive and prone to develop skin tumours in sun-exposed areas. Biochemical and genetic studies have demonstrated that nucleotide excision repair, the most versatile DNA repair mechanism, is deficient in XP cells, leading to ultraviolet-induced hypermutagenesis and a predisposition of XP patients to cancer. Cloning of XP genes responsible for the disease, together with the poor efficacy of classical pharmacological treatments, have motivated approaches towards cutaneous gene therapy of the XP. The author's group have successfully reconstructed XP skin in vitro from XP keratinocytes and fibroblasts. More recently, the possibility to fully revert the phenotype of XP keratinocytes after retrovirus-mediated transfer of the adequate wild-type XP gene in XP keratinocytes was demonstrated. Reconstruction of genetically corrected XP skin in vitro constitutes a new hope toward cutaneous gene therapy of the XP.