Patients with malignant tumor treated with immunotherapy have received significant clinical benefits over the years. Immune checkpoint blocking agents, such as anti-cytotoxic T-lymphocyte-associated protein-4 (anti-CTLA-4) and anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibodies, have produced impressive clinical results in different types of cancer. T-cell immunoglobulin and mucin domain-3 (TIM-3), another immune checkpoint, could inhibit cancer immunity. Recent studies have highlighted that TIM-3 has an important role to play in T-cell exhaustion and correlates with the outcome of anti-PD-1 therapy. Targeting TIM-3 might be a promising approach for cancer immunotherapy. Here, we review the role of TIM-3 in cancer and clinical trials with TIM-3 inhibitors.