Background: Onychomycosis is by far the most common finger or toe nail fungal infectious disease caused by dermatophytes, non-dermatophytic molds or yeast. It accounts for 50% of the total nail disorders, and affects patients physically, socially, and psychologically and can seriously influence their quality of life. Objectives: Oral antifungals are routinely used to treat the nail fungal disease; however oral therapy is associated with severe side effects and longer treatment times. In recent years, drug delivery directly into the nail or nail bed has gained attention and various topical products have been tested that can cure the disease when applied topically or transungually. Nevertheless, drug penetration into and through the nail is not straightforward and requires chemicals to improve its permeability or by applying physical stress to promote drug penetration into and through the nail. Topics covered: This lucid review presents an overview of various causes of onychomycosis, current therapeutic approaches, and efforts aimed at increasing the permeability of nails through various strategies such as chemical, physical and mechanical methods for permeation enhancement. Conclusion: Various strategies have been proposed for the treatment of onychomycosis, however, much research into a more precise and effective therapy is still required.