**Abstract**

Monoclonal antibodies that inhibit "immune checkpoint" through programmed cell death-1 and its ligand (PD-1/PD-L1) blockage have proven remarkable therapeutic action toward a range of cancer types. Hence, immunotherapy, binding the immune system to act against malignant tumors, has generated encouraging outcomes in clinical practice. Nevertheless, the robust advantage is not observed in a large number of patients. Recognizing patients that will probably respond and using therapies covering a larger number of patients necessitate an enhanced understanding of the biological action of PD-1 and cytotoxic T lymphocyte antigen (CTLA) at the cell level and reviewing the performed clinical studies and their outcomes to recognize the accumulating proof of its clinical significance. In this chapter, we will discuss and review the clinical and preclinical data regarding Immune Checkpoint Inhibitors PD-1/PD-L1 to recognize the advances and challenges of their implication in clinical practice.

**Keywords:** immune checkpoint, PD-1, PD-L1, target therapy, immunotherapy, resistance
