Continuous monitoring of clinical biomarkers offers the exciting possibility of new therapies that use biomarker levels to guide treatment in real time. This review explores recent progress toward this goal. We initially consider measurements in body fluids by a range of analytical methods. We then discuss direct tissue measurements performed by implanted sensors; sampling techniques, including microdialysis and ultrafiltration; and noninvasive methods. A future directions section considers analytical methods at the cusp of clinical use.