Lung cancer remains the leading cause of cancer-related deaths among men and women in the civilized world. Although there have been major improvements over the recent decades in surgical techniques and the role of chemotherapy-radiotherapy in the treatment of non-small cell lung cancer (NSCLC), the long-term outlook for these patients has not changed significantly. The median survival for patients with advanced-stage NSCLC treated with platinum-based chemotherapy is a disappointing 8-10 months. In current clinical practice, chemotherapy is used as a combined modality with radiotherapy as an adjuvant or neoadjuvant therapy. Moreover, combination chemotherapy is regarded as the standard care in the treatment of unresectable locally advanced (stage IIIb), metastatic (stage IV), or recurrent disease. The recent developments in the treatment of NSCLC have been focused on the emerging role of adjuvant therapy in the early stages of NSCLC. The clinical activity of pemetrexed, a multitargeted antifolate anticancer agent, as a second-line chemotherapy agent and the impact of new biological agents, such as bevacizumab and erlotinib, have been investigated in phase III trials in the first- and second-line setting. Even though these options have been available in the last few years, there is a clear need for improvement in the current standard of care. No definite survival benefit has yet been demonstrated. An abundant amount of research is still required in the field of lung cancer therapy with well-designed clinical trials and appropriate patient selection.