Immune checkpoint molecules are regulators of immune activation playing a key role in immune homeostasis. We aimed to review the role of immune checkpoints in cancer. Cancer emerges when the immune checkpoint mechanisms are activated to suppress the antitumor immune response. This has led to the development of several checkpoint regulators that are currently being tested in clinical trials or have been approved for some cancers. There are two types of immune regulatory function, i.e., stimulatory and inhibitory. Among the most important immune checkpoints for regulation in immunotherapy are programmed death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene-3 (LAG-3), T immunoglobulin and ITIM area (TIGIT), and B and T cell lymphocyte attenuators (BTLA) mostly expressed on the tumor cells and/or tumor-infiltrating immune cells. Immune checkpoints play a crucial role in cancer drug development. Immunotherapy focused on immune checkpoints is regularly tolerated more than conventional chemotherapy, and favorable responses are frequently seen. However, the medical advantages have been mostly restricted to a subset of cancer patients.