Over the last years, several new systemic cancer therapy strategies have been introduced to turn the growing insights of molecular aberrations involved in the development and progression of lung cancer into better treatment options fort the patients. This review presents some of the most important biological targets and biomarkers relevant in the treatment of non-small cell lung cancer. Especially EGFR mutations, anti-angiogenesis, multi kinase inhibition, vascular disrupting agents, vaccines, m-TOR inhibitors, TRAIL inhibition and several biomarkers are highlighted including current study results.