Chimeric antigen receptor T (CAR-T) technology is the pinnacle of modern immunology, system biology, synthetic biology and cellular engineering. It is the powerful new player of cancer therapy since the concept of adoptive cell therapy. Clinical success of CAR-T cells targeting antigen unique to B cell leukemia has made it the focus of new development in cancer therapy. The latest success is reported in a clinical case of using CAR-T cells to treat pediatric acute lymphoblastic leukemia. However, the major challenges are to make CAR-T cells a reliable, controllable, safe and effective platform that could apply to diverse cancer types including solid tumors. In this review we summarize the recent research progress to tackle the challenges and discuss the broader application of CAR-T cells beyond cancer in the context of genome editing era.