The population groups predisposed to onychomycosis and factors associated with a poor response to antifungal therapy may be subdivided into (a) genetic, (b) environmental, (c) systemic conditions, (d) local nail characteristics, and (e) other miscellaneous items. By paying attention to the scenarios that may lead to a suboptimal response to the therapy and a higher probability of relapse of the onychomycosis, it may be possible to improve the overall cost-effectiveness of treatments for onychomycosis. Besides attempting to achieve a cure when treating onychomycosis it is important to take steps to prevent reinfection with fungal organisms.