This review has traced chemotherapy of coccidioidomycosis from its unsuccessful beginnings through the present time. Although in vitro susceptibilities give initial impressions of activity of many drugs, and although animal studies identify the diseases targeted for initial trials, ultimately it is the patient in whom the benefits and risks of a new agent must be weighed. For this reason, considerations have been limited to clinical studies, with no review of animal data or immunologic forms of therapy such as transfer factor. In this review, amphotericin B has been found to be the first active antifungal agent in coccidioidomycosis. Although responses clearly occurred, even in meningitis, the vagaries of disease and investigators prevented a really hard assessment of how many patients really were "cured" versus how many relapsed again and again. Responses were given in broad ranges and the term "remission" came to be considered a more accurate definition for this illness than "cure." The azole antifungals, though fungistatic, gave us, for the first time, the ability to treat a patient indefinitely with an oral preparation; the advantages of this cannot be overstated. Although all of these drugs act by similar mechanisms, the differences in potency, pharmacokinetics and toxicities have brought fluconazole and itraconazole to the fore. Which of the two is superior (if either is) cannot be defined with the limited data available. The role of SCH39304 is, at present, unclear. Other agents such as nikkomycin and modified polyenes may enter a role in clinical evaluation of coccidioidomycosis, but for the next five years the drugs described in the preceding pages, or combinations, are likely to constitute the pharmaceutical arsenal against C. immitis. While we now have much more to offer the heirs of Domingo Escurra and Jose Furtado-Silveira than gentian violet and carbolic acid, we still have response rates of less than 75% for extrameningeal disease and we have not yet identified a drug that will guarantee a cure without later relapse. There is still a way to go.