Whole-blood biosensors and point-of-care testing created a unique paradigm in medical diagnostics in the 1980s, when liver and heart transplant centers, as well as operating rooms and other critical care areas implemented whole-blood analysis to provide rapid test results in 2 to 5 minutes. Rising expectations, patient-focused hospitals, and managed care intensify the need for immediate decisions at the point of care. The guidelines promote consensus priorities, multidisciplinary teamwork, fiscal coordination, and collaborative practice during this phase of rapid change. Four primary principles and accompanying guideline objectives are optimization (patient outcomes, medical linkages, integrated diagnostic synthesis, therapeutic turnaround time, test clusters, and critical limits), hybridization (strategic modalities, economic effectiveness, and testing double right arrow monitoring), quality (quality improvement, clinical performance, risk reduction and academics and accreditation), and consistency (results communication and error minimization, and reference intervals and standardization). Whole-blood analysis and point-of-care testing help facilitate temporal optimization, optimize diagnostic-therapeutic processes, and improve patient outcomes in critical care.