As the use of epidermal growth factor receptor inhibitors becomes more widespread, increasing data are being collected regarding both efficacy and toxicity. Cutaneous toxicities are emerging not only as the most relevant class-related events, but also as potentially important markers of response to therapy. Although a follicular eruption is the most frequent cutaneous manifestation of epidermal growth factor receptor inhibition, ingrown nails, paronychia, and xerosis and desquamation of the digits, all of which occur in a substantial number of patients, require attention from treating oncologists and dermatologists. These nail disorders are mostly mild to moderate in severity, but, if not properly managed, can result in significant pain and interfere with activities of daily living. Descriptions of the nail and periungual toxicities associated with epidermal growth factor receptor inhibitor therapy and prevention and treatment strategies are presented.