Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Early recognition is crucial to improve outcomes, but conventional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) show limited diagnostic accuracy. This video performs a narrative review of the literature on sepsis biomarkers, with a focus on their biological role, diagnostic performance, clinical applicability, and limitations. Particular attention was given to presepsin (P-SEP) and monocyte distribution width (MDW), which have recently gained relevance. Several novel biomarkers—including lipopolysaccharide-binding protein (LBP), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), mid-regional pro-adrenomedullin (MR-proADM), neutrophil gelatinase-associated lipocalin (NGAL), Proenkephalin (PENK), and circulating microRNAs—have been studied, though most remain investigational. Among them, P-SEP shows rapid kinetics and correlation with disease severity, while MDW, derived from routine complete blood count, offers encouraging sensitivity and cost-effectiveness in emergency settings. Both biomarkers appear practical and potentially valuable for early sepsis detection. This video concludes that P-SEP and MDW emerge as the most promising biomarkers for timely sepsis recognition and risk stratification. Further validation and standardization are required to include them into routine clinical practice.