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The lymphatic system consists of a collection of lymphatic vessels connected to lymph nodes which filter lymph fluid that gets collected throughout the body. Lymph nodes filter lymph via specialized white blood cells that destroy and remove microorganisms, malignant cells, damaged cells, and foreign particles.  The lymphatic vessels and lymph nodes, along with the thymus, tonsils, and spleen, serve a vital function for the removal of interstitial fluid from tissue and development and maintenance of the immune response. Lymph fluid ultimately returns to the venous circulation. Lymph nodes are present throughout the body.  The head and neck region contains over 300 lymph nodes, of which include the supraclavicular lymph nodes.[1] This paper will focus on the supraclavicular lymph nodes and their anatomical relations, drainage, physiological variations, surgical considerations, and clinical significance in the context of malignancy and other pathology.