Understanding the physiology and function of the nail unit and its potential avenues of invasion, and properly identifying invading organisms are two key aspects of using the newer therapies available for the treatment of onychomycosis. This article discusses the most common pathologies of onychomycosis, as classified by the sites of entry of the invading fungi. Susceptibility factors leading to infection are also discussed. Obtaining proper tissue samples, using appropriate tests and culture media, and accurately interpreting test results are all paramount to correct identification of the invading organism and, in turn, to effective prescribing. When fungal-growth results do not support the clinical symptoms, or if a more specific identification of the organism is required, additional diagnostic tests are available and are outlined here.