The article discusses the development of novel immune checkpoint targets beyond PD-1 and CTLA-4, which are crucial for cancer immunotherapy. These new targets include LAG-3, TIM-3, TIGIT, VISTA, B7-H3, and BTLA. These molecules have shown promise in preclinical studies and clinical trials, offering potential for more effective cancer treatments. The review outlines the structure, expression, and current understanding of these immune checkpoints, as well as their clinical applications and future prospects. It highlights the importance of these targets in enhancing immune responses against tumors and overcoming resistance to existing therapies. The article also discusses the mechanisms by which these checkpoints regulate T cell activity and the potential of combining them with existing immune checkpoint inhibitors to improve therapeutic outcomes. Despite the promising results, challenges remain in identifying ligands for some of these targets and in developing effective clinical strategies. The review emphasizes the need for further research to fully understand the therapeutic potential of these new immune checkpoint targets.The article discusses the development of novel immune checkpoint targets beyond PD-1 and CTLA-4, which are crucial for cancer immunotherapy. These new targets include LAG-3, TIM-3, TIGIT, VISTA, B7-H3, and BTLA. These molecules have shown promise in preclinical studies and clinical trials, offering potential for more effective cancer treatments. The review outlines the structure, expression, and current understanding of these immune checkpoints, as well as their clinical applications and future prospects. It highlights the importance of these targets in enhancing immune responses against tumors and overcoming resistance to existing therapies. The article also discusses the mechanisms by which these checkpoints regulate T cell activity and the potential of combining them with existing immune checkpoint inhibitors to improve therapeutic outcomes. Despite the promising results, challenges remain in identifying ligands for some of these targets and in developing effective clinical strategies. The review emphasizes the need for further research to fully understand the therapeutic potential of these new immune checkpoint targets.