The standard of care for the evaluation of axillary nodal involvement remains complete lymph node dissection. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this long-held paradigm; indeed, several leading institutions already reserve complete axillary dissection for patients with metastasis to the SLN. In addition to reviewing the literature, this chapter describes our lymphatic mapping experience at the H Lee Moffitt Cancer Center and Research Institute with 1147 breast cancer patients. Our results, in addition to a meta-analysis of data from 12 institutions comprising an additional 1842 patients undergoing complete axillary dissection, demonstrate that SLN biopsy is an accurate method of axillary staging. Although the results from small series may exaggerate the probability of false negative results, the risk of nodal disease based on tumor size and other risk factors should be evaluated when considering the results of SLN sampling.