Immunotherapy has recently become widely used in lung cancer. Many oncologists are focused on cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1). Immunotherapy targeting the PD-1/PD-L1 checkpoints has shown promising efficacy in non-small cell lung cancer (NSCLC), but questions remain to be answered. Among them is whether the simultaneous inhibition of other checkpoints could improve outcomes. Lymphocyte-activation gene-3 (LAG-3) is another vital checkpoint that may have a synergistic interaction with PD-1/PD-L1. Here we review the LAG-3 function in cancer, clinical trials with agents targeting LAG-3 and the correlation of LAG-3 with other checkpoints.