The identification of variations or mutations in genes encoding proteins that are involved in drug processing or metabolism can provide key information relevant to differential responses to therapeutic agents in specifi c genetic populations groups. It is well accepted that genetic variability (functional polymorphisms) may explain the failure of therapies and/or serious adverse side effects during and after treatment. Therefore, there is enormous interest in identifying these variants and determining their clinical relevance. In this regard, the main focus of pharmacogenomics is the study of inherited variations in genes that modulate drug response and their infl uence in predicting patient response to a specifi c treatment. For this purpose, pharmacogenomics integrates genomic information and technologies driving drug discovery and developing large-scale genomic studies to identify genetic variations. These fi ndings may provide benefi ts in designing therapies more targeted to specifi c diseases, maximizing therapeutic effects, decreasing adverse reactions, and developing better methods to determine effective drug dosages. In addition to the anticipated benefi t of personalized medicine, the identifi cation of genetic markers may also infl uence the lifestyle, environment, and diet of those individuals with high susceptibility to develop a particular disease(s) and to prevent or delay the development of diseases. This chapter will focus on mutations and the variety of polymorphisms that may be associated with therapy resistance for people with different types of lung diseases such as chronic obstructive pulmonary disease (COPD), tuberculosis (TB), idiopathic pulmonary fi brosis (IPF), pulmonary arterial hypertension (PAH), and interstitial lung damage (ILD). In fact, insights from recent evidences strongly support the notion that pharmacogenomics will be essential in improving innovative genomic-based therapies based on the genomic profi les of patients.