Tyrosinase inhibitors have been developed to partially interfere with melanin synthesis and have been utilized both medicinally for the amelioration of lesions in numerous hyperpigmentary diseases (melasma, lentigos, post inflammatory/wound healing hyperpigmentation, etc.) and cosmetically for general skin lightening. However, current commercially available inhibitors are ineffective or may cause various side effects (erythema, scarring, vitiligo) and possibly carcinogenic. Therefore, deoxyArbutin (dA) has been developed as an effective and safe tyrosinase inhibitor. The hydroxyl groups on the polar tail ring of arbutin were removed to create dA, thus facilitating its transepidermal penetration. dA was a more effective inhibitor of mushroom tyrosinase than hydroquinone, exhibiting a 10-fold lower Ki. In cultures of normal human melanocytes, tyrosinase activity was reduced 20% after 5 days of dA treatment and normalized 5 days after removing treatment. In a pigmented skin Guinea Pig model, the L-value was significantly raised in a dose dependant manner by 3 weeks of dA application and skin color normalized 8 weeks after halting application. Various metabolic and safety analyses were performed with optimal results. The efficacy of dA on human skin was demonstrated in three models; human zenografts on SCID mice, a clinical study assessing constitutive skin color, and a clinical study assessing facultative skin color. Second generation molecules of dA, including Fluro-dA and the L isoform of dA, were more effective than dA as tyrosinase inhibitors. dA has recently been brought to market.