Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each persons own genetic makeup. The field of pharmacogenomics in regards to severe infections is a growing and im-portant field in modern medicine. Severe infections, like severe community acquired pneumonia (CAP) or sepsis have a great impact in morbidity and mortality and consume a great amount of sanitary resources. Those infections have not been analyzed properly under the point of view of pharmacogenomics. The genomes of both the host and the pathogen are key points in this field. There are specific mutations in the host genome associated with adverse outcomes (genes of antigen recognition molecules, pro-inflammatory cytokines, anti-inflammatory cytokines, and effectors molecules). Those muta-tions could define a genetic profile of high risk patient in whom a specific treatment should be added urgently. In addition, some adverse effects to antibiotics can be predicted performing genetic t esting. As the concept one-drug-fits-all approach is no longer appropriate in medicine, the genetic profile is discussed like useful tool to make important clinical decisions regarding treatment and to design clinical trials. Moreover, the genome of the host could help us to know if nonresponding patients to vaccine are genetically pre-programmed to be nonresponders or whether failure to respond is a random event. On the other hand, genome of pathogen could have advantages in the clinical management establishing a definitive diag-nosis, determining antimicrobial resistance and/or following the response to treatment.