Lung tumors continue to be the most frequent cause of cancer-related death in Western industrialized countries. The development of new chemotherapeutic substances that are directed specifically against oncogenic pathomechanisms of non-small cell lung cancer represents a promising therapeutic approach. Meanwhile treatment measures are being employed for pulmonary adenocarcinomas that target the epidermal growth factor receptor and transforming EML4-ALK fusion protein. However, these therapies benefit almost exclusively those patients who have never smoked and manifest relatively rare subtypes of adenocarcinomas. In contrast, targeted therapeutic options for squamous cell carcinomas of the lung frequently found in smokers are still limited, although amplifications of the fibroblast growth factor receptor 1 have recently been identified as possible therapeutic targets in this patient population. This contribution provides an overview of the underlying pathomechanisms and molecular diagnostics needed for treatment stratification.