This chapter explores the use of lab-on-a-chip technologies to investigate questions in cellular mechanotransduction. Cells in culture respond to signals that are both soluble (provided by growth factors) and insoluble (provided by adhesion to the extracellular matrix or neighboring cells). Both classes of cues are critical for cell survival and function, but in contrast to soluble cues, insoluble cues have been experimentally hard to control. To address these challenges, chip-based microfabrication technologies have been developed to engineer the physical microenvironment of cells in culture and are now being used to study cellular mechanotransduction. This chapter will focus on the labon- a-chip based methods developed to control the physical input contributed by the microenvironment and to measure the output response of cells to their surroundings.