Sepsis remains the leading cause of death in infants and children worldwide. Prompt diagnosis and monitoring of infection is pivotal to guide therapy and optimize outcomes. No single biomarker has so far been identified to accurately diagnose sepsis, monitor response and predict severity. We aimed to assess existing evidence of available sepsis biomarkers, and their utility in pediatric population. C-reactive protein and procalcitonin remain the most extensively evaluated and used biomarkers. However, biomarkers related to endothelial damage, vasodilation, oxidative stress, cytokines/chemokines and cell bioproducts have also been identified, often with regard to the site of infection and etiologic pathogen; still, with controversial utility. A multi-biomarker model driven by genomic tools could establish a personalized approach in future disease management.