Targeted therapies have transformed lung cancer treatment by offering more precise and effective options compared to traditional chemotherapy. These therapies target specific molecular pathways involved in cancer growth, survival, and metastasis, leading to improved outcomes and quality of life. Key molecular drivers in non-small cell lung cancer (NSCLC) include EGFR mutations, ALK rearrangements, FGFR, and KRAS mutations. EGFR mutations are common in adenocarcinoma (ADC) and are associated with better responses to EGFR inhibitors. First-generation EGFR tyrosine kinase inhibitors (TKIs) like gefitinib and erlotinib showed initial promise but were later surpassed by second and third-generation TKIs, which offer better efficacy and fewer side effects. Second-generation TKIs such as afatinib and dacomitinib have shown improved progression-free survival (PFS) in clinical trials. Third-generation TKIs like AZD9291 and CO1686 are irreversible inhibitors that target both the wild-type and mutated EGFR, with minimal toxicity. ALK rearrangements are another important target, with drugs like crizotinib and ceritinib showing significant efficacy. However, resistance mechanisms, including mutations in the ALK kinase domain and activation of alternative pathways, can limit long-term benefits. Novel ALK inhibitors are under investigation to overcome resistance. Angiogenesis inhibitors like bevacizumab and nintedanib have also been used to improve outcomes in NSCLC. Other promising targets include BRAF, PI3K, MET, and ROS1, with corresponding inhibitors in clinical trials. Despite these advancements, challenges remain, including drug resistance, tumor heterogeneity, and the need for more effective diagnostic tools. Liquid biopsies and next-generation sequencing are emerging as valuable tools for molecular profiling. The introduction of targeted therapies has also changed the design of clinical trials, allowing for more efficient and targeted approaches. While new agents are rapidly being developed, their integration into clinical practice requires regulatory approval and careful consideration of patient selection and treatment strategies. Overall, targeted therapies represent a significant step forward in personalized lung cancer treatment.Targeted therapies have transformed lung cancer treatment by offering more precise and effective options compared to traditional chemotherapy. These therapies target specific molecular pathways involved in cancer growth, survival, and metastasis, leading to improved outcomes and quality of life. Key molecular drivers in non-small cell lung cancer (NSCLC) include EGFR mutations, ALK rearrangements, FGFR, and KRAS mutations. EGFR mutations are common in adenocarcinoma (ADC) and are associated with better responses to EGFR inhibitors. First-generation EGFR tyrosine kinase inhibitors (TKIs) like gefitinib and erlotinib showed initial promise but were later surpassed by second and third-generation TKIs, which offer better efficacy and fewer side effects. Second-generation TKIs such as afatinib and dacomitinib have shown improved progression-free survival (PFS) in clinical trials. Third-generation TKIs like AZD9291 and CO1686 are irreversible inhibitors that target both the wild-type and mutated EGFR, with minimal toxicity. ALK rearrangements are another important target, with drugs like crizotinib and ceritinib showing significant efficacy. However, resistance mechanisms, including mutations in the ALK kinase domain and activation of alternative pathways, can limit long-term benefits. Novel ALK inhibitors are under investigation to overcome resistance. Angiogenesis inhibitors like bevacizumab and nintedanib have also been used to improve outcomes in NSCLC. Other promising targets include BRAF, PI3K, MET, and ROS1, with corresponding inhibitors in clinical trials. Despite these advancements, challenges remain, including drug resistance, tumor heterogeneity, and the need for more effective diagnostic tools. Liquid biopsies and next-generation sequencing are emerging as valuable tools for molecular profiling. The introduction of targeted therapies has also changed the design of clinical trials, allowing for more efficient and targeted approaches. While new agents are rapidly being developed, their integration into clinical practice requires regulatory approval and careful consideration of patient selection and treatment strategies. Overall, targeted therapies represent a significant step forward in personalized lung cancer treatment.