A variety of out-of-plane deformation patterns have been observed for two-dimensional (2D) materials including ripples, wrinkles, buckles, scrolls, folds, tents, and bubbles due to their extra-low bending rigidity. Among them, the micro- and nanoscale bubbles arising from the deformation of the atomically thin membrane by gases, liquids, and solids trapped underneath 2D materials were frequently observed. On the one hand, the presence of bubbles may severely deteriorate the performance of 2D material devices because of the obstructed charge, photon, and phonon transport across the interface. On the other hand, these bubbles offer a novel avenue to explore the intrinsic mechanical parameters (e.g., Young’s modulus and bending rigidity) of 2D materials as well as their interfacial properties (e.g., shear stress and adhesion energy). Furthermore, these bubbles with stable and controllable morphology also act as effective knobs to tune the electronic and photonic performance of various 2D materials. This review highlights the recent progress on the 2D material bubbles, which will be helpful for measurement of the mechanical properties of ultrathin 2D materials and the applications of developing 2D material devices.