The most frequent cancer related deaths have been associated with lung cancer. The subtypes, Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancers (SCLC), respond to chemical drugs and radiotherapy. NSCLC (60%) express membrane epidermal growth factor receptor (EGFR). The cell signalling pathway induced by EGFR has been attributed as a key reason for lung cancer progression. There are many FDA approved drugs available for the treatment which primarily includes EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, or EGFR neutralizing antibody, necitumumab. However, the reports suggest that EGFR can undergo further mutation in tyrosine kinase domain which makes the cells resistant to the ongoing treatment. Alternate signalling pathways may get activated accompanied by epithelial mesenchymal transition and imbalanced microRNAs that contribute towards resistance. Epigenetic changes in lung cancer also offer dynamic targets for cancer therapy. The agents targeting epigenetic changes can be combined with chemotherapy or other-directed therapy so that effective dose and hence toxicity is reduced with enhanced efficacy. Micro-RNAs are the largest class of the gene regulators that regulate the cancer genes. Inhibiting or replacing the cancer-causing miRNAs can be potential targets for cancer treatment. Researchers have also worked on immunotherapy drugs like nivolumab, pembrolizumab and atezolizumab, which reverse the inhibitory mechanism of the immune response. New findings from recent trails provide an optimistic perspective on the progress towards the better treatment of lung cancer.