The effective management of patients in intensive care units, operating rooms, and emergency rooms requires frequent measurement of a select group of analytes, preferably at or near the patient's bedside. Tests recognized as being essential for such management include blood gases and related variables (pH, pO2, pCO2, HCO3-, hematocrit/hemoglobin, O2 saturation), electrolytes (Na+, K+, Ca2+, Cl-), and in some cases, certain metabolites (glucose, lactate, urea, creatinine). This report describes the measurement principles, practical instrumental designs, analytical performance, and limitations of several newer electrochemical sensor-based approaches useful for in vitro determination of these species in undiluted whole-blood samples. Considerable attention is given to the most recent advances in ion-selective electrode technology as they relate to blood gas and electrolyte determinations. Similar attention is given to modern enzyme-electrode techniques, which are useful for direct measurements of metabolites in whole blood. The challenges of integrating these new analytical methods into convenient, multi-analyte, user-friendly, bedside or stat-lab instruments are also discussed.