Onychomycosis, a persistent fungal infection affecting the toenails and fingernails, can interfere with standing, walking, and exercising. Associated physical impairments can result in paresthesia, pain, discomfort, and loss of manual dexterity. Patients may also suffer from loss of self-esteem and social interaction. A definitive diagnosis is crucial for effective treatment, because many other skin and nail disorders mimic onychomycosis. Diagnosis involves microscopic potassium hydroxide preparation, cultures, nail biopsy, and histologic analysis. Treatment can include topical and systemic antifungal therapies as well as nonpharmaceutical methods. This paper discusses pathophysiology, diagnosis, and treatment options for this common nail dystrophy, including the newer antifungal medications now available.