Immunotherapy based on T cells modified with a chimeric antigen receptor (CAR) has been demonstrated as a promising strategy for cancer treatment. CARs are artificial recombinant receptors that combine the specificity of a target-specific antibody with the T cell activation domains. Currently, CARs are generally categorized into three generations. The first-generation CARs mediates activation of modified T cells via the CD3ζ signaling domain. The Second-generation CARs contain costimulartory signaling domains derived from T cell costimulatory molecules such as CD28, the most commonly used in CAR construction. Besides CD28, other costimulatory molecules such as 4-1BB, OX40, ICOS and CD27 may be included with important roles in regulating T cell proliferation, survival and antitumor functions. The third-generation CARs have been constructed consisting of two costimulatory molecular signaling regions.