The recent discovery of immune checkpoints inhibitors, especially 
anti-programmed cell death protein 1 (PD-1) and anti-programmed cell death 
protein ligand 1 (PD-L1) monoclonal antibodies, has opened new scenarios in the 
management of non-small cell lung cancer (NSCLC) and this new class of drugs has 
achieved a rapid development in the treatment of this disease. However, 
considering the costs of these drugs and the fact that only a subset of patients 
experience long-term disease control, the identification of predictive 
biomarkers for the selection of candidates suitable for treatment has become a 
priority. The research focused mainly on the expression of the PD-L1 receptor on 
both tumor cells and/or immune infiltrates determined by immunohistochemistry 
(IHC). However, different checkpoint inhibitors were tested, different IHC 
assays were used, different targets were considered (tumor cells, immune 
infiltrates or both) and different expression thresholds were employed in 
clinical trials. In some trials the assay was used prospectively to select the 
patients, while in other trials it was evaluated retrospectively. Some confusion 
emerges, which makes it difficult to easily compare the literature data and to 
translate them in practice management. This mini-review shows the possibilities 
and pitfalls of the PD-L1 expression to predict the activity and efficacy of 
anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.