In patients with community-acquired pneumonia, traditional criteria of infection based on clinical signs and symptoms, clinical scoring systems, and general inflammatory indicators (for example, leukocytosis, fever, C-reactive protein and blood cultures) are often of limited clinical value and remain an unreliable guide to etiology, optimal therapy and prognosis. Procalcitonin is superior to other commonly used markers in its specificity for bacterial infection (allowing alternative diagnoses to be excluded), as an indicator of disease severity and risk of death, and mainly as a guide to the necessity for antibiotic therapy. It can therefore be viewed as a diagnostic, prognostic, and perhaps even theragnostic test. It more closely matches the criteria for usefulness than other candidate biomarkers such as C-reactive protein, which is rather a nonspecific marker of acute phase inflammation, and proinflammatory cytokines such as plasma IL-6 levels that are highly variable, cumbersome to measure, and lack specificity for systemic infection. Elevated levels of pro-adrenomedullin, copeptin (which is produced in equimolar amounts to vasopressin), natriuretic peptides and cortisol are significantly related to mortality in community-acquired pneumonia, as are other prohormones such as pro-atrial natriuretic peptide, coagulation markers, and other combinations of inflammatory cytokine profiles. However, all biomarkers have weaknesses as well as strengths. None should be used on its own; and none is anything more than an aid in the exercise of clinical judgment based upon a synthesis of available clinical, physiologic and laboratory features in each patient.