One case of keratitis ichthyosis deafness (KID) syndrome and two cases of bullous ichthyosiform erythroderma (BIE) were treated with systemic acitretin. The severe hyperkeratotic lesions improved dramatically with acitretin therapy in the KID case. Substantial improvement of the palmoplantar keratoderma was also observed. During follow-up, laboratory results remained within normal limits and no skeletal abnormalities were detected. The two cases with BIE also showed good responses to acitretin. Long-term follow-up of these cases showed that signs and symptoms were well under control and no adverse effects were noted.