Sentinel lymph node biopsy (SLNB) is based on the hypothesis that the sentinel lymph node (SLN) reflects the lymph-node status and a negative SLN might allow complete axillary lymph node dissection (ALND) to be avoided. Past and current sentinel lymph node clinical trials for breast carcinoma and melanoma address the prognostic and therapeutic utility of SLN dissection (SLND). This technique has already become a standard of care for breast cancer patients and select patients with melanoma. However, it is still important to discuss current techniques and some controversies. This article reviews these issues as well as current guidelines for treatment and management of patients with various findings on SLNB.