Improving existing means of sentinel lymph node identification in non-small cell lung cancer will allow for molecular detection of occult micrometastases that may cause recurrence in early stage non-small cell lung cancer. Furthermore, targeted application of chemical and biological cytotoxic agents can potentially improve outcomes in patients with lymph node (LN) metastases. "Therapeutic Sentinel Lymph Node Imaging" incorporates these modalities into a single agent thereby identifying which LNs harbor tumor cells and simultaneously eradicating metastatic disease. In this review, we summarize the novel preclinical agents for identification and treatment of tumor bearing LNs and discuss their potential for clinical translation.