Over the last couple of decades, molecular diagnostics have played an increasing role in drug development. Especially within oncology, more and more drugs are being developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. Not only do these assays support the development process but also the use of the drugs after regulatory approval as an important treatment decision tool. When these predictive biomarker assays are linked to a specific drug, they are called companion diagnostics. Furthermore, these assays are also considered an important element in the realization of precision medicine. Today, 21 different drugs have obtained US FDA approval together with a companion diagnostic assay, and the requirement for testing is part of their regulatory labeling. More than half of these drugs are for treatment of non-small cell lung cancer (NSCLC). With the approval of the different programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors, for the treatment of advanced stage NSCLC, a new class of predictive biomarker assays-complementary diagnostics-has emerged. Until now, 3 immune checkpoint inhibitors have obtained regulatory approval for treatment of NSCLC, and they all have a biomarker assay linked to their use. However, only for pembrolizumab, the PD-L1 immunohistochemical (IHC) 22C3 pharmDx assay has status as a companion diagnostic. For nivolumab and atezolizumab, the assays PD-L1 IHC 22C3 pharmDx and Ventana PD-L1 (SP142) have status as complementary diagnostics, which means that there are no requirements for testing included in the labeling for these drugs. Here, the authors discuss the clinical performance of the different IHC PD-L1 expression assays including the selection of the clinical cutoff values.