Tyrosinase plays an essential role in melanogenesis. Excess production of melanin can be a reason for hyperpigmentation skin disorders in mammals and enzymatic browning in plant-derived foods. Catalyzing the rate-limiting step of melanin synthesis, tyrosinase has become the most studied target for melanogenesis inhibition. Over the past ten years, a number of synthetic thiosemicarbazone derivatives have been reported to possess strong tyrosinase inhibitory properties with IC50 values below 1 μM, placing them among the most potent tyrosinase inhibitors. This review gives an overview of tyrosinase activity and describes tyrosinase-inhibiting thiosemicarbazones in terms of their structure-activity relationships, kinetics of enzyme inhibition and mechanism of action. Results of the studies of thiosemicarbazones as tyrosinase inhibitors from over 20 research articles have been analyzed, compared and summarized in the present paper. Using thiosemicarbazones as tyrosinase inhibitors is a promising approach in developing anti-melanogenetic agents for skin-whitening cosmetics and anti-browning agents for food.