After the initial attempt of biologic therapies in GO (Antonelli et al., 1992; Baschieri et al., 1997), more recently, etanercept (that blocks the TNF-mediated inflammatory responses), TCZ (that acts against the IL-6 receptor), and RTX (that acts against CD20) have proven to be useful and safe therapeutic options in refractory GO treatment. This evidence concerns the gene TNF and geroderma osteodysplastica.