The chapter discusses the advancements in targeted therapies for lung cancer, particularly focusing on the role of precision medicine. It highlights the evolution from cytotoxic chemotherapy to targeted agents that specifically inhibit molecules involved in cancer cell growth and survival. The introduction of targeted therapies has significantly changed the treatment paradigm for non-small cell lung cancer (NSCLC), especially in patients with specific molecular subtypes such as EGFR mutations, ALK rearrangements, and KRAS mutations. For EGFR mutations, the chapter details the development and clinical trials of first-generation (gefitinib and erlotinib) and second-generation (afatinib and dacomitinib) EGFR tyrosine kinase inhibitors (TKIs). These agents have shown significant improvements in progression-free survival (PFS) and overall survival (OS) in various trials, particularly in patients with EGFR-mutated lung ADCs. The chapter also discusses the role of EGFR-directed monoclonal antibodies, such as cetuximab, panitumumab, nimotuzumab, and necitumumab, which, while not yet widely used, show promise in clinical trials. The chapter further explores the treatment of ALK rearranged tumors with crizotinib, ceritinib, alectinib, and other novel ALK inhibitors. These agents have demonstrated efficacy in both crizotinib-naïve and pre-treated patients, with some showing activity in crizotinib-resistant cases. The discussion includes the mechanisms of drug resistance, such as mutation of the ALK tyrosine kinase domain and amplification of the *EML4–ALK* gene. Additionally, the chapter covers the use of antiangiogenic drugs like bevacizumab, nintedanib, and ramucirumab, which target circulating VEGF or VEGFR, and their impact on PFS and OS in NSCLC patients. Finally, the chapter touches on promising new targets and agents, including BRAF inhibitors, PI3K inhibitors, MET inhibitors, ROS1 inhibitors, and HER2 inhibitors, highlighting ongoing research and clinical trials. The conclusion emphasizes the importance of molecular testing and the dynamic nature of cancer, where tumor heterogeneity and drug adaptation pose significant challenges.The chapter discusses the advancements in targeted therapies for lung cancer, particularly focusing on the role of precision medicine. It highlights the evolution from cytotoxic chemotherapy to targeted agents that specifically inhibit molecules involved in cancer cell growth and survival. The introduction of targeted therapies has significantly changed the treatment paradigm for non-small cell lung cancer (NSCLC), especially in patients with specific molecular subtypes such as EGFR mutations, ALK rearrangements, and KRAS mutations. For EGFR mutations, the chapter details the development and clinical trials of first-generation (gefitinib and erlotinib) and second-generation (afatinib and dacomitinib) EGFR tyrosine kinase inhibitors (TKIs). These agents have shown significant improvements in progression-free survival (PFS) and overall survival (OS) in various trials, particularly in patients with EGFR-mutated lung ADCs. The chapter also discusses the role of EGFR-directed monoclonal antibodies, such as cetuximab, panitumumab, nimotuzumab, and necitumumab, which, while not yet widely used, show promise in clinical trials. The chapter further explores the treatment of ALK rearranged tumors with crizotinib, ceritinib, alectinib, and other novel ALK inhibitors. These agents have demonstrated efficacy in both crizotinib-naïve and pre-treated patients, with some showing activity in crizotinib-resistant cases. The discussion includes the mechanisms of drug resistance, such as mutation of the ALK tyrosine kinase domain and amplification of the *EML4–ALK* gene. Additionally, the chapter covers the use of antiangiogenic drugs like bevacizumab, nintedanib, and ramucirumab, which target circulating VEGF or VEGFR, and their impact on PFS and OS in NSCLC patients. Finally, the chapter touches on promising new targets and agents, including BRAF inhibitors, PI3K inhibitors, MET inhibitors, ROS1 inhibitors, and HER2 inhibitors, highlighting ongoing research and clinical trials. The conclusion emphasizes the importance of molecular testing and the dynamic nature of cancer, where tumor heterogeneity and drug adaptation pose significant challenges.