The review discusses the recent advances and future directions in cancer immunotherapy targeting TIGIT, a newly identified checkpoint receptor. TIGIT is highly expressed on various immune cells, including CD4+ T cells, CD8+ T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). It has been associated with NK cell exhaustion and mediates T cell exhaustion. CD155, the primary ligand of TIGIT, is a potential target for immunotherapy due to its interaction with TIGIT. Anti-TIGIT therapy has shown promise in preclinical studies, particularly in combination with anti-PD-1 agents, but clinical trials have had mixed results. Tiragolumab, an anti-TIGIT antibody, failed in two recent trials for advanced lung cancer. The review highlights the current developments in TIGIT-based cancer immunotherapy, discusses the characteristics and functions of TIGIT, and explores potential reasons for the clinical failures of anti-TIGIT treatments. It also reviews preclinical studies and clinical trials of anti-TIGIT agents, emphasizing the need for further research to identify effective biomarkers and combination therapies.The review discusses the recent advances and future directions in cancer immunotherapy targeting TIGIT, a newly identified checkpoint receptor. TIGIT is highly expressed on various immune cells, including CD4+ T cells, CD8+ T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). It has been associated with NK cell exhaustion and mediates T cell exhaustion. CD155, the primary ligand of TIGIT, is a potential target for immunotherapy due to its interaction with TIGIT. Anti-TIGIT therapy has shown promise in preclinical studies, particularly in combination with anti-PD-1 agents, but clinical trials have had mixed results. Tiragolumab, an anti-TIGIT antibody, failed in two recent trials for advanced lung cancer. The review highlights the current developments in TIGIT-based cancer immunotherapy, discusses the characteristics and functions of TIGIT, and explores potential reasons for the clinical failures of anti-TIGIT treatments. It also reviews preclinical studies and clinical trials of anti-TIGIT agents, emphasizing the need for further research to identify effective biomarkers and combination therapies.