While PD-L1 by immunohistochemistry has been successfully employed as a companion diagnostic for several therapies across a handful of indications, PD-L1 is only one potential biomarker for showing a predictive response. PD-L1 does not provide a complete depiction of the tumor and it is widely documented that some PD-L1 negative patients have responded positively to immunotherapy. As more combination therapies are examined, more informative markers will need to guide when and how a treatment or combinations of treatment should be considered.