The emergence of new novel therapeutic agents which directly target molecules that are uniquely or abnormally expressed in cancer cells (molecular targeted therapy, MTT) has changed dramatically the treatment of cancer in recent years. The clinical benefit associated with these agents is typically limited to a subset of treated patients, who in many cases are defined by a specific genomic mutations and expression lesion within their tumor cells. All these new therapy modalities represent new challenges to radiologists as their mechanism of action and side effect profiles differ from conventional chemotherapy agents. In this article we will discuss radiological patterns of response to molecular targeted therapies MTT in lung cancer, typical and atypical radiological responses of targeted molecular therapy for other intra thoracic malignancies, cardiopulmonary toxicity and other side effects of molecular targeted therapy MTT in the thorax.