Since the approval of the first epidermal growth factor receptor (EGFR) inhibitor for the treatment of non-small cell lung cancer (NSCLC) in 2003, great strides have been made in this field of targeted therapy to address the global burden of lung cancer, which is the most diagnosed and the leading cause of cancer-related death worldwide. This thesis investigates the pharmacological aspects of older generations of EGFR inhibitors, including their mechanism of action, pharmacokinetics, clinical efficacy, and adverse effects, as well as the resistance mechanisms of tumors to these drugs. Despite improvements in therapy due to the emergence of osimertinib and other third generation EGFR inhibitors, resistance remains a global concern which mandates further research. Therefore, many therapeutic strategies which have been heavily investigated, as well as novel agents such as antibody drug conjugates, vaccines, monoclonal antibodies, and ultimately, fourth generation EGFR inhibitors, have been described in this work, aiming to shed light on the advances that can revolutionize the landscape of NSCLC therapy.