In keratinization disorders, the living keratinocytes of the deeper epidermis change into dead corneocytes of horny layer, where they are stuck together by intercellular lipids. Desquamation, proliferation and / or adherent capacity of cells are abnormal, and epidermis may thicken or the skin surface may become xerotic and scaly. These keratinization disorders can be localized or generalized. In this chapter, retinoid use in keratinization disorders is reviewed. In the recent years, the molecular mechanisms of keratinization disorders have become clearer, including keratin mutations, cell adherent enzymes, and molecules. Synthetic retinoids, including isotretinoin, acitretin and topical retinoids such as tazaroten, and isotretinoin have been used for the treatment of a variety of keratinization disoders such as ichthyosis and palmoplantar keratoderma. Relapse following cessation of therapy and the possible side effects of the retinoids for an otherwise benign condition are factors that limit their general use. Topical treatments must be used regularly in keratinization disorders. Low-dose retinoid therapy is recommended as maintenance. Regular biochemical analysis, skeletal examinations and prevention of pregnancy are requested during systemic therapy.