BACKGROUND: There is no general agreement as to what constitutes cure or treatment success in onychomycosis. Regulatory guidelines differ in the United States and Europe, and outcomes reported in clinical trials do not consistently report secondary endpoints. METHODS: We reviewed definitions of onychomycosis cure to develop a less stringent and more practical approach to assess improvement and treatment success. RESULTS: Complete cure (totally clear nail and mycologic cure) remains an important regulatory standard. Mycologic cure (negative fungal culture and negative potassium hydroxide) is the only consistently reported outcome in clinical trials, however the potential for discrepancies between microscopy and culture can be problematic. We propose a more practical approach to assessing improvement in infected nails that relies on both physician and patient input in a similar fashion to other skin diseases. CONCLUSIONS: Treatment success should be based on both physician and patient assessment of improvement in the affected toenails and negative fungal culture.