It has been almost thirty years since the first publication on microphthalmia-associated transcription factor (MITF) in 1993. MITF, which plays an important role in the melanogenesis process, is an interesting target for melanoma therapy, due to its associates with melanoma survival. MITF promotes melanoma cell proliferation, whereas the sustained suppression of MITF expression causes aging. MITF contributes to differentiation, which involves breaking out of the cell cycle and triggering a melanogenesis, and this function appears to often persist during melanoma development given the frequently observed high pigmented lesions, even in the late stages of melanoma. Several drugs that could inhibit MITF e.g. histone deacetylase inhibitors, such as sodium butyrate and trichostatin A, have been proven could suppress M-MITF expression in melanoma cells. H1-receptor antagonists, particularly loratadine, could downregulate MITF and tyrosinase in melanocytes. Some plants can inhibit MITF e.g Gentiana veitchiorum Hemsl., Thymelaea hirsuta, Argania spinosa L. In this review, we update the information about MITF and describe the mechanism of its inhibitors in preventing melanogenesis.