Despite recent advances with new chemotherapeutic agents and target therapies, the prognosis of NSCLC remains poor. Recent results from clinical trials of immunotherapeutic agents, especially with immune checkpoint inhibitors, make this approach very exciting in NSCLC. Ipilimumab is a monoclonal antibody directed against cytotoxic T-lymphocyte antigen 4 that is able to stimulate the antitumour immune response by promoting T-cell activation. We have reviewed the literature and have described the most important results obtained with ipilimumab in NSCLC in recent trials with a specific focus on its peculiar toxicity profile and pattern of response. Trials ongoing with ipilimumab are also reported. The results from clinical trials with ipilimumab are promising. Some important issues in the near future will be to identify prognostic and predictive biomarkers to select patients who could benefit from this drug. Further studies are warranted to understand how to combine ipilimumab with other anticancer strategies.