Purpose The role of procalcitonin in guiding antibiotic therapy is reviewed. Summary Procalcitonin is a prohormone for calcitonin, which is secreted by the parafollicular cells of the thyroid gland. The biological activity of procalcitonin is significantly different from calcitonin and is believed to be part of the complex inflammatory cascade of the immune system. Procalcitonin has been shown to be elevated in bacterial infections but not in viral infections or other inflammatory conditions. The first published study that suggested that procalcitonin levels increased in the presence of bacterial infection was conducted in France in the early 1990s. Numerous studies have been conducted using procalcitonin-guided therapy to reduce antibiotic use. These studies were performed in one of three clinical settings: outpatient primary care (two multicenter, noninferiority studies of patients with upper- and lower-respiratory-tract infections), emergency room and inpatient (five studies in patients with chronic obstructive pulmonary disease, exacerbation, bronchitis, or community-acquired pneumonia), and the intensive care unit (ICU) (two studies in medical ICU patients and two in postoperative ICU patients with infection or sepsis). Based on the findings of these studies, a cutoff value of 0.25 μg/L in non-ICU patients or of 0.5 μg/L in ICU patients seems appropriate for making a decision about the initiation and discontinuation of antibiotic therapy. In patients with a significantly elevated baseline procalcitonin level, a subsequent drop of >80% appears to be reasonable for discontinuing antibiotics. Conclusion Published evidence supports the use of procalcitonin as a biomarker of bacterial infection that can be used to reduce antibiotic exposure.