The inflammatory response depends on several factors, including pathogenicity and duration of the stimulus, and also the balance between inflammatory and anti-inflammatory responses. Studies conducted in animal models, different racial groups, families, twins, and adopted children, have presented evidence of the importance of genetics in severe infections. A genetic finding could help to explain why the systemic inflammation in community-acquired pneumonia becomes a life-threatening disease for some people, and yet has only a mild effect on others. Particularly important are the Single-Nucleotide Polymorphisms (SNPs). The increasing availability of data on SNP and the great diversity of clinical phenotypes have stimulated the emergence of numerous studies of association between SNPs in community-acquired pneumonia. The innate immune response is the body’s first line of defense that prevents the invasion and spread of pathogens during the first hours after infection. This immediate protection against microorganisms includes a number of mechanisms. First, the host has to recognize the invading pathogen and induce its destruction, either by complement-mediated lysis, or phagocytosing it; at the same time, the host must develop an inflammatory response, and finally, should trigger an anti-inflammatory response that is capable to restore the homeostatic balance. Each of these processes may be affected by polymorphisms of genes involved, which can result in susceptibility or resistance to infection. The immediate future of genetic association studies in infectious diseases will continue with case-control designs and the use of DNA microarray that simultaneously analyze 500,000 polymorphisms. This approach will help to select candidate genes for association studies in humans and to identify new routes or pathways, which will undoubtedly revolutionize vaccine and antimicrobial development.