For decades, clinicians have seen no therapeutic advances for SCLC, including no FDA-approved targeted therapies; recently, immune checkpoint blockade has emerged as a promising new option for the treatment of relapsed SCLC (including recent FDA approval of nivolumab in the third-line setting) and may soon represent the frontline standard of care in combination with chemotherapy. However, we need to uncover biomarkers to guide patient selection and develop novel approaches to enhance response to immunotherapies.