Adaptive immunotherapy with T-cells is being evaluated as therapy for a number of malignancies and viral infections. Genetic modification of infused T-cells has been used for several years to track such cells, to redirect and augment the immune response towards tumors, and to provide a means of ablating infused T-cells should adverse effects occur. New strategies to target T-cells to tumors and to genetically modify them to make them resistant to tumor evasion mechanisms are being evaluated in preclinical models.