Background: We report a comprehensive overview of current Chronic Obstructive Lung Disease (COPD) therapies and discuss the development of possible new pharmacological approaches based on “new” knowledge. Specifically, sensitivity/resistance to corticosteroids is evaluated with a special focus on the role of gene mutations in drug response. Objective: Critically review the opportunities and the challenges occurring in the treatment of COPD. Conclusion: Findings from “omics” trials should be used to learn more about biological targeted drugs, and to select more specific drugs matching patient’s distinctive molecular profile. Specific markers of inflammation such as the percentage of eosinophils are important in determining sensitivity/resistance to corticosteroids. Specific gene variations (Single nucleotide polymorphisms: SNPs) may influence drug sensitivity or resistance. Clinicians working in a real-world need to have a suitable interpretation of molecular results together with a guideline for the treatment and recommendations. Far more translational research is required before new results from omics techniques can be applied in personalized medicine in realworld settings.