Human skin aging results from intrinsic and extrinsic factors. Uneven pigmentation is one of the major changes of extrinsic aging. Many compounds have been tested for depigmenting activity but only a few are actually used by the cosmetic industry, which is continually looking for new ingredients. In this study, the trends in the use of skin depigmenting ingredients in a panel of anti-aging formulations commercialized in the Portuguese pharmacy market were analyzed, by comparing the composition of the products marketed in 2011 with products launched or reformulated in 2018 (59% and 74%, respectively). The analysis of the top 12 ingredients put forward three novelties for 2018: tranexamic acid, bakuchiol, and 4-butylresorcinol. Regarding their mechanisms of action, tranexamic acid inhibits melanin synthesis through inhibition of the plasminogen/plasmin system. Bakuchiol depigmenting efficacy was attributed to the ability to block both α-melanocyte-stimulating hormone and tyrosinase activation, while 4-butylresorcinol exerts its action through the inhibition of both tyrosinase and tyrosinase-related protein-1 (TRP-1). Industry-optimized and efficient synthetic methodologies that embrace green chemistry, reducing the environmental impact, are commonly used. This analysis aims to bring insights to both formulators, involved in the development of depigmenting cosmetic products, and chemists performing the synthesis of new and existing compounds intended for this purpose.