Procalcitonin (PCT) is a circulating polypeptide produced in response to bacterial infections. Studies conducted in the Intensive Care Unit (ICU) setting have demonstrated its utility as a biomarker of bacterial infection and sepsis. Thus, PCT is widely used to distinguish between sepsis and SIRS, and to guide antibiotic therapy. At present sepsis represents a frequent diagnosis among patients admitted to Internal Medicine (IM) departments. Basing on the knowledge derived from ICU studies, the use of PCT has become routine in non-intensive wards, contributing to improve the management of sepsis. However, some differences between the two populations of patients - the IM being older, affected by multiple chronic comorbidities and lacking of invasive monitoring - could limit the generalizability of ICU results. Most of the studies on PCT conducted in the IM setting have focused on chronic obstructive pulmonary disease, pneumonia and sepsis. Although PCT represents one of the best biomarker available in routine clinical practice, there are uncertainties on the optimal cut-offs to be used for starting or discontinuing antibiotic treatment in patients with suspected bacterial infection or sepsis, for predicting outcome and on the role of PCT variations during antibiotic treatment. Moreover, several diseases can produce an elevation of PCT levels, thus producing false positive results. This represents a narrative review summarizing current evidences on PCT for the management of sepsis in an Internal Medicine wards, highlighting differences with ICU, with a special focus on the role of PCT variations as predictor of outcomes in non-ICU wards.