Onychomycosis is a common infection of the nail unit that is usually caused by a 
dermatophyte (tinea unguium) and most frequently affects toenails in adults. In 
most cases, onychomycosis is associated with limited treatment options that are 
effective in achieving complete clearance in many cases. In addition, recurrence 
rates are high in the subset of treated patients who have been effectively 
cleared, usually with an oral antifungal agent. There has been a conspicuous 
absence of medical therapies approved in the United States since the 
introduction of topical ciclopirox (8% nail lacquer), with no new effective 
agents introduced for more than 10 years. Fortunately, newer agents and 
formulations have been under formal development. While patients might prefer a 
topical therapy, efficacy with ciclopirox 8% nail lacquer, the only available 
agent until the very recent approval of efinaconazole 10% solution, has been 
disappointing. The poor therapeutic outcomes achieved with ciclopirox 8% nail 
lacquer were not unexpected as the cure rates achieved in the clinical trials 
were unimpressive, despite concomitant nail debridement, which was an integral 
part of the pivotal trials with ciclopirox 8% nail lacquer. Efinaconazole 10% 
solution and tavaborole 5% solution are new topical antifungals specifically 
developed for the treatment of dermatophyte onychomycosis. In Phase 3 clinical 
trials, both newer agents were applied once daily for 48 weeks without 
concomitant nail debridement. Mycologic cure rates with efinaconazole 10% 
solution are markedly superior to what was achieved with ciclopirox 8% nail 
lacquer. To add, they appear to be nearly comparable to those achieved with oral 
itraconazole in pivotal clinical trials. However, it is important to remember 
that direct comparisons between different studies are not conclusive, are not 
generally considered to be scientifically sound, and may not be entirely 
accurate due to differences in study design and other factors. Well-designed and 
properly powered head-to-head studies are needed in order to draw definitive 
conclusions about efficacy comparisons between therapies, at least based on 
academic and regulatory standards. Although tavaborole 5% solution is in an 
earlier phase of development for onychomycosis, treatment success rates reported 
thus far for both efinaconazole 10% solution and tavaborole 5% solution are 
superior to ciclopirox 8% nail lacquer. As a result, a new era of onychomycosis 
appears to be upon us that incorporates topical therapy more effectively than in 
the past. Not only may these newer topical agents provide viable monotherapy 
alternatives to oral therapy for onychomycosis, topical therapy for 
onychomycosis that is effective, well tolerated, and easy to use may also find a 
role in combination therapy, and/or as continued therapy after initial clearance 
to reduce recurrence or re-infection.