The primary goals of oncologic therapy are the compassionate care of cancer patients, eradication of disease, and palliation of symptoms. Advances in various targeted therapies such as highly conformal and image-guided radiotherapy techniques, sentinel lymph node dissection, and molecularly targeted agents hold the promise of allowing those goals to be reached with fewer treatment-related complications. Unfortunately, certain side effects remain problematic due to the inability to completely avoid injuring normal tissues. Lymphedema, a chronic condition that occurs as a result of the body's inability to drain lymph fluid from the tissues, is a common treatment-related side effect experienced by cancer patients. In this review, many of the important aspects of lymphedema with which clinicians who treat cancer patients should be familiar are outlined, including the anatomy, pathophysiology, diagnosis, and management of this condition. The authors also identify some of the resources available both to cancer patients with lymphedema and to the clinicians who treat them. It is hoped that this review will convey the importance of the early identification and management of this incurable disorder because this is essential to minimizing its complications. CA Cancer J Clin 2009;59:8–24. © 2009 American Cancer Society.