Immunotherapy has changed the face of cancer treatment in metastatic melanoma. Clinical trials using tumor infiltrating lymphocytes (TIL) to recognize and mediate regression of tumor cells have demonstrated objective responses. One of the limitations of TIL is the inability to access tumors in patients or the presence of too few tumor infiltrating lymphocytes present in the tumors once resected. This has stimulated researchers to engineer methods to convert normal lymphocytes into tumor targeted T-cells. One method of doing so is through genetic modification of peripheral autologous lymphocytes with genes encoding T-cell receptors. Genetically engineered T-cells can broaden the opportunity for the use of T-cell immunotherapy in melanoma and other cancer patients. It also offers the possibility of improving the T-cell efficacy with the introduction of additional genes giving them an advantage over TIL.