Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to an infection. Bacterial infection progressing to sepsis is associated with high morbidity, mortality, reduction of quality of life in survivors and health care costs. The course and outcome of sepsis is highly heterogeneous and depends on the causative pathogen, on the timing and varies from patient to patient. The individual outcome is significantly influenced by various complex host-and pathogen-related factors. Increasing rates of multi-drug resistant bacteria further complicate the diagnostic process and clinical management and may lead to treatment failure. Rapid and reliable diagnosis of sepsis and the identification of the causative infective agent are critical steps towards a successful treatment outcome. Therefore, patients with sepsis would greatly benefit from personalized diagnostic assessment and treatment strategies evaluating and integrating the host and the pathogen.