Potassium iodide was discovered in the 19th century and still remains as one of the more effective and most prescribed treatments for sporotrichosis. No new drugs have been evaluated in large randomized clinical trials in comparison with standard or alternative treatments for sporotrichosis during the last decades. The emergence of disseminated sporotrichosis in AIDS patients has uncovered the need for more effective treatments. Sporotrichosis is only a public health problem in a few geographical areas, mostly located in developing countries; and its usually harmless history could explain the limited investment in sporotrichosis treatment research. Better understanding of the virulence factors, such as the melanization process, could reveal new potential drug targets.