Between the DNA sequences of two randomly-selected human genomes, which consist of over 3 billion base pairs and twenty five thousand genes, there exists only 0.1% variation and 99.9% sequence identity. During the last couple of decades, extensive genome-wide studies have investigated the association between single-nucleotide polymorphisms (SNPs), the most common DNA variations, and susceptibility to various diseases. Because the immune system's primary function is to defend against myriad infectious agents and diseases, the large number of people who escape serious infectious diseases underscores the tremendous success of this system at this task. In fact, out of the third of the global human population infected with Mycobacterium tuberculosis during their lifetime, only a few people develop active disease, and a heavy chain smoker may inexplicably escape all symptoms of chronic obstructive pulmonary disease (COPD), lung cancer, and other smoke-associated lung diseases. This may be attributable to the genetic makeup of the individual(s), including their SNPs, which provide some resistance to the disease. Pattern recognition receptors (PRRs), transcription factors, cytokines and chemokines all play critical roles in orchestrating immune responses and their expression/activation is directly linked to human disease tolerance. Moreover, genetic variations present in the immune-response genes of various ethnicities may explain the huge differences in individual outcomes to various diseases and following exposure to infectious agents. The current review focuses on recent advances in our understanding of pulmonary diseases and the relationship of genetic variations in immune response genes to these conditions.