Miniaturized whole blood biosensors, patient-focused hospitals, and rising expectations of patients and physicians are shifting laboratory diagnostics to the point of care. Expanding transplantation and intensive care are increasing the need for rapid test results. Whole blood analysis improves accuracy, eliminates centrifugation, reduces response time, and conserves blood volume. Several hand-held, and over 20 portable or transportable whole blood instruments are now available. Criteria for instrument evaluation include test menus, point-of-care features, analysis time, on-site performance, and information integration. Whole blood analyzers measure several vital indicators (pO₂, pCO₂, pH, hematocrit, K⁺, Ca²⁺, Na⁺, Cl^-, glucose, and lactate) simultaneously in less than 2 min with less than 200 μl of whole blood. Other in vitro tests are available (Mg^2*, osmolality, CO₂ content, urea nitrogen, β-hydroxybutyrate, hemoglobin, coagulation) or under development (HCO₃^- phosphorus). Some can be monitored in vivo (O₂ saturation, pO₂, pCO₂, pH, glucose) or ex vivo. The clinical impact is demonstrated by ionized calcium, now established in importance for cardiac and neurologic problems, and ionized magnesium, a promising new measurement. The hybrid laboratory (a composite of conventional clinical laboratory and patient-focused testing), performance maps, and quality paths facilitate implementation of new whole blood analyzers for optimal support of cardiac and critical care, and improved patient outcomes (prospects).