Over the last decades we have witnessed substantial progress in the first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). While several targeted therapies entered the therapeutic arena for patients harbouring oncogenic driver mutations, the treatment for patients with non-oncogene driven NSCLC remained largely chemotherapy based. In recent years however, also the treatment paradigm for these patients underwent a transformation. In fact, convincing data generated by a long list of randomized trials, established immune checkpoint inhibition as a new therapeutic strategy for an ever-growing proportion of NSCLC patients. Within a couple of years immune checkpoint blockade moved from the second line setting to first-line therapy and broadened its scope from advanced to locally advanced NSCLC. As such, it turned the first-line treatment of advanced NSCLC into a competitive battlefield of crucial importance. Currently, three immunotherapeutic strategies have proven their worth in the first line treatment of patients with advanced, non-oncogene driven NSCLC: the use of PD-(L)1 inhibitors in monotherapy, combining PD-(L)1 inhibitors with chemotherapy, and combining PD-(L)1 inhibitors with other immune checkpoint inhibitors (mainly anti CTLA-4). In this article we will review the most recent clinical data generated with these three therapeutic strategies and provide updates on the biomarkers that can guide the choice for one of these options in the individual patient.