Diabetes mellitus may be associated with serious sequelae, such as renal disease, retinopathy, and diabetic foot. A recent large prospective study has shown that onychomycosis is among the most significant predictors of foot ulcer. As the severity of onychomycosis may be associated with the length of time the individual has had the infection, early intervention is advisable owing to the progressive nature of the fungal infection. If left untreated, toenails can become thick, causing pressure and irritation, and thus act as a trigger for more severe complications. In the treatment of onychomycosis, compliance and drug interactions are important considerations, as diabetic patients frequently take concomitant medications. Terbinafine and itraconazole have been investigated for the treatment of onychomycosis in diabetic patients and have been shown to have efficacy and safety profiles comparable to those in the nondiabetic population. Data from clinical trials and postmarketing surveillance suggest that drug interactions resulting in hypoglycemia may not be an important issue when itraconazole and terbinafine are used to treat diabetic patients receiving concomitant hypoglycemic medications. Patient advice and education in improved foot care are an integral part of onychomycosis management, and help achieve long-term cure and reduce the complications of diabetic foot.