INTRODUCTION: Small cell lung cancer (SCLC) is a tumor with a poor prognosis, often diagnosed in an advanced stage. Despite aggressive treatment of early and locally advanced disease, SCLC often relapses. First line chemotherapy provides good response rates in advanced disease, but progression free and overall survival are limited. New drugs such as some targeted therapies and immune therapies are promising in SCLC. Areas covered: In this review, we discuss the preclinical rationale and trial data for targeted therapies and immune therapies in SCLC, with a specific focus on clinical trials. Expert commentary: Lack of identification of clear prognostic and predictive biomarkers has limited the advances in treatment efficacy. This has most likely been the main cause of failure for compounds tested so far. Due to the highly mutational profile and the rapid growth pattern of SCLC, immunotherapy combined with chemotherapy seems the most promising treatment option. Concerning targeted agents, achievements made so far are small, but DLL3-antibodies or combinations of PARPi and immunotherapy could be very promising. These promising strategies also need testing in limited disease.