Luckily, most infections resolve spontaneously. Sometimes, however, they become more severe. If, as a result of the infection, organs dysfunction, this is called sepsis. In this thesis, the trajectory of patients with a severe infection through the Dutch acute care chain was studied, with specific attention to possible targets for optimisation of care. The included studies showed that patients with a severe infection are present throughout the entire acute care chain and that general practitioners fulfil an important role. Different parameters are used in the decision whether or not to refer a patient to the hospital, among which a patient’s medical history, vital signs and the healthcare provider’s gut feeling. Unfortunately, vital signs were not measured consistently and there appeared to be opportunities for improvement in the documentation of sepsis and of a sense of urgency. In order to keep improving care, these items deserve the attention of all involved healthcare providers.