International data from 2002 report 10.9 million new cases of cancer and 6.7 million cancer deaths. Chemotherapy is an essential component in the multidisciplinary management of most cancers. Cutaneous reactions to chemotherapeutics are common and may contribute significantly to the morbidity, and rarely to the mortality, of patients undergoing such treatments. Recognition and management of these reactions is important to provide optimal care. This article aims to present the most common cutaneous reactions to frequently used chemotherapies and provides management guidelines. A MEDLINE search from 1966 through June 2005 was conducted to identify reports of common cutaneous toxicities with systemic chemotherapy and their appropriate management. An analysis of our literature search is presented in review form outlining common chemotherapy-related cutaneous reactions and their management, as well as the chemotherapeutics responsible for the cutaneous toxicity. Chemotherapy-related cutaneous toxicity includes generalized rashes such as the spectrum between erythema multiforme and toxic epidermal necrolysis, and site-specific toxicity such as mucositis, alopecia, nail changes, extravasation reactions, or hand-foot syndrome. Most of the toxicity is reversible with chemotherapy dose reductions or delays. Certain toxicities can be effectively treated or prevented, allowing optimal delivery of chemotherapy (e.g. premedications to prevent hypersensitivity, prophylactic mouthwashes to prevent mucositis). Newer non-chemotherapeutic targeted therapies such as epidermal growth factor receptor inhibitors (e.g. gefitinib, cetuximab) may also be associated with cutaneous toxicity and can be distressing for patients. Recent data suggest that skin toxicity associated with these agents may correlate with efficacy. Cutaneous toxicity occurs frequently with chemotherapy and non-chemotherapeutic biologic therapies. Early recognition and treatment of the toxicity facilitates good symptom control, prevents treatment-related morbidity, and allows continuation of anti-cancer therapy.