Epidermal growth factor receptor (EGFR) inhibitors are associated with unique and dramatic dermatologic side effects. Cetuximab, erlotinib, and gefitinib have been approved for patients with colorectal and non–small cell lung cancer refractory or intolerant to chemotherapy. Our aim was to describe key clinical features of common dermatologic adverse reactions among EGFR inhibitors, focusing mainly on skin toxicity, as well as to discuss the pathology, possible causes, and suggested treatments for these reactions. The most commonly encountered adverse effect was a mild skin toxicity characterized by a sterile follicular and pustular rash that may be treated empirically and usually does not require treatment modification. Although the precise mechanism for development of rash is not well defined, it is related to inhibition of EGFR-signaling pathways in the skin, and may serve as visible markers of anti-tumor activity and therapeutic efficacy. Secondary adverse reactions seen with anti-EGFR therapy include xerosis, pruritus, paronychia, hair abnormality, and mucositis.