Small-cell lung cancers (SCLC) are aggressive malignancies, however, characterized by high primary chemosensitivity. Unfortunately, for the vast majority of patients, relapse is the rule with emergence of secondary resistance mechanisms. In the era of molecular targeted therapies, characterization of a number of molecular abnormalities has encouraged implementation of several clinical trials. This literature review summarizes the various pharmacological approaches used in SCLC to improve survival in localized and extensive forms of the disease. Initial trials with molecular targeted therapies have not been able to improve clinical outcome compared to the standard etoposide-cisplatin chemotherapy regimen in extensive forms. However, new targets continue to be identified and many treatments are currently being assessed, including blockade of angiogenesis, signal transduction, cell cycle or induction of apoptosis.