A biomarker is a molecule that can be measured in a biological sample in an objective, systematic, and precise way, whose levels indicate whether a process is normal or pathological. Knowing the most important biomarkers and their characteristics is the key to precision medicine in intensive and perioperative care. Biomarkers can be used to diagnose, in assessment of disease severity, to stratify risk, to predict and guide clinical decisions, and to guide treatments and response to them. In this review, we will analyze what characteristics a biomarker should have and how to ensure its usefulness, and we will review the biomarkers that in our opinion can make their knowledge more useful to the reader in their clinical practice, with a future perspective. These biomarkers, in our opinion, are lactate, C-Reactive Protein, Troponins T and I, Brain Natriuretic Peptides, Procalcitonin, MR-ProAdrenomedullin and BioAdrenomedullin, Neutrophil/lymphocyte ratio and lymphopenia, Proenkephalin, NefroCheck, Neutrophil gelatinase-associated lipocalin (NGAL), Interleukin 6, Urokinase-type soluble plasminogen activator receptor (suPAR), Presepsin, Pancreatic Stone Protein (PSP), and Dipeptidyl peptidase 3 (DPP3). Finally, we propose an approach to the perioperative evaluation of high-risk patients and critically ill patients in the Intensive Care Unit (ICU) based on biomarkers.