Clinical and mycologic results for fluconazole strongly support its efficacy for the management of fingernail and toenail onychomycosis caused by dermatophytes. Its excellent tolerability and convenient once-weekly dosing schedule should promote high patient compliance. Patients who are compliant with their treatment regimen are more likely to have clinical success. Furthermore, clinical improvement occurs early in therapy. A distinct advantage of fluconazole is its once-weekly dosing regimen, which helps manage patient expectations for how quickly they will see a visual improvement in their nails. Drug interactions may not be as significant a concern for fluconazole as with other azoles. It is also important to note that relapse rates are particularly low (about 2.6% for fingernails and 4% for toenails), which are the lowest rates reported in NDA pivotal trials of antifungal agents for onychomycosis. The papers comprising this supplement provide detailed descriptions of the key studies carried out to assess the pharmacokinetics, efficacy, and safety of fluconazole in patients with toenail and fingernail onychomycosis. The studies include two pharmacokinetic evaluations of fluconazole, one in patients with fingernail onychomycosis and one in patients with toenail onychomycosis. Of the three clinical trials reviewed, two evaluated the effects of different fluconazole doses (150, 300, or 450 mg, once weekly) in patients with either fingernail or toenail onychomycosis, and the third assessed the effect of treatment duration on clinical and mycologic outcome in patients who received 450 mg fluconazole once weekly for toenail onychomycosis. Based on the results of these studies, once-weekly dosing of fluconazole for 3 months in fingernails and for 6 months in toenails is effective in treating onychomycosis. The results of these studies provide a clear clinical and pharmacokinetic profile for fluconazole in patients with onychomycosis and suggest strongly that it will be a very important agent for use in patients with this common and difficult to treat fungal infection.