There is limited data regarding generic medication prices. Recent studies have shown price changes at the retail level, but much is not known about the pharmaceutical supply chain or price changes at the manufacturer level. We sought to examine the extent of price changes for topical generic medications. A comprehensive review of average wholesale prices (AWPs) and manufacturers of topical generics and available corresponding branded medications was conducted for 2005 and 2016. A total of 51 topical chemical entities were examined. Between 2005 and 2016, the AWP of topical generic medications increased by 273% and the AWP of topical branded medications increased by 379%. The topical generic with the greatest price change increased by 2529%. Eight of the top 20 topical generic medications with the greatest increases in AWP also had an increase in the number of manufacturers. These findings are not generalizable to medications used in other areas of medicine. Topical generic prices are rapidly increasing at the manufacturer level. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.