Programmed death ligand 1 (PD-L1) is the principal ligand of programmed death 1 (PD-1), a coinhibitory receptor that can be constitutively expressed or induced in myeloid, lymphoid, normal epithelial cells and in cancer. Under physiological conditions, the PD-1/PD-L1 interaction is essential in the development of immune tolerance preventing excessive immune cell activity that can lead to tissue destruction and autoimmunity. PD-L1 expression is an immune evasion mechanism exploited by various malignancies and is generally associated with poorer prognosis. PD-L1 expression is also suggested as a predictive biomarker of response to anti-PD-1/PD-L1 therapies; however, contradictory evidence exists as to its role across histotypes. Over the years, anti-PD-1/PD-L1 agents have gained momentum as novel anticancer therapeutics, by inducing durable tumour regression in numerous malignancies including metastatic lung cancer, melanoma and many others. In this review, we discuss the immunobiology of PD-L1, with a particular focus on its clinical significance in malignancy.