Cellular mechanical properties have been observed to have important implications for pathogenesis and pathophysiology. These observations have led to the recent development of a unique class of biomarkers: mechanical biomarkers. Compared with the traditional biochemical-based biomarkers (e.g., antibodies), mechanical biomarkers have many advantages such as label-free, low cost, convenient maintenance, and reduced assay time. In the past few years, there has been an increasing effort to exploit cellular mechanical biomarkers in microfluidic devices. This trend makes sense because microfluidic devices often feature structures that have characteristic lengths similar to those of cells, which renders them uniquely capable of probing and utilizing mechanical biomarkers. In this Focus article, we discuss a few examples of mechanical biomarker-based microfluidic applications. We believe that these examples are just the tip of the iceberg and that the full potential of mechanical biomarkers in microfluidic-based diagnostics and therapeutics has yet to be revealed.