Small-cell lung cancer is an aggressive form of lung cancer that, overall, remains the most common cause of cancer death in the US. Some advances have been made in the treatment of small-cell lung cancer using cytotoxic chemotherapeutic agents but no truly targeted therapies are available as of yet. At present, research is focused on finding therapies that can target the specific molecular mechanisms responsible for the survival, growth and metastasis of the tumor thereby improving responses to chemotherapy and minimizing toxicity. Several new agents, such as angiogenesis inhibitors and regulators of apoptosis, have reached clinical testing and multiple others are in preclinical trials. Some of these will be discussed in this review.