Breast cancer treatment is recognized as the most common cause of secondary lymphedema (LE) in the developed countries of the world. LE occurs as both an acute and chronic health condition in which significant and persistent swelling is associated with an abnormal accumulation of protein-rich fluid. The impact of LE is significant on a wide range of daily activities and survivorship quality of life. Measurement and quantification of LE has been problematic despite the fact that various methods have been used to measure limb volume (LV). Perhaps in part because of difficulties in measurement and diagnosis, the reported incidence of LE varies greatly among persons treated with surgery and radiation for breast cancer. Through increased measurement accuracy, LE incidence and prevalence following current therapeutic approaches for breast cancer treatment cancer will be better understood, and more informed decisions about risk factors, treatment interventions, and recovery will be made. Further identification of epidemiological and clinical factors associated with risk and incidence will provide the necessary foundation for preventive intervention. Bilateral measurements at pre-op and over time are necessary to assess LV changes during follow-up, as it is important as part of the differential diagnosis to note whether volume change has occurred in the affected limb alone or in both limbs. Application of rigorous measurement protocols, assessment of symptom experience, and establishment of a data base on bilateral LV at pre-op for later comparison are essential components of a solid foundation for intervention studies. Through multidisciplinary collaboration with rigorous scientific approaches feasible to be carried out in the clinical setting, we have the opportunity to better target risk factors for development of LE, design data-based interventions, and improve post-treatment quality of life.