Abstract: The immunotherapeutic agents targeting programmed death-1/programmed cell death-ligand 1(PD-1/PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) have been applied to clinical practice and are gaining increasing clinical significance. However, as limited population could benefit from these agents, it is imperative to identify new therapeutic targets and explore the appropriate immunoregulatory mechanisms to improve the therapeutic effects for malignant tumors. From the perspectives of specific immunity and non-specific immunity, this paper reviews the origin of the immune checkpoints, the basic studies, as well as the latest results of the completed and ongoing clinical studies, involving the specific immune checkpoints including T cell immunoglobulin mucin 3(TIM–3), lymphocyte activation gene-3(LAG-3), V-domain Ig suppressor of T-cell activation(VISTA), etc, and the non-specific immune checkpoints including killer cell immunoglobulin-like receptor(KIR), indoleamine 2, 3-dioxygenase(IDO) and CD47, in an attempt to provide evidences for clinical and basic studies.