While static methods are often essential to make a material suited to a specific application, by permanently altering its properties, dynamic ones potentially enable their real-time modulation, paving the way for the development of reconfigurable devices.Within this context, strain engineering has historically been regarded as a "static" tuning method, which exploited the crystal deformations induced by the juxtaposition of materials with different lattice constants to manipulate the properties of semiconductor heterostructures [1] and improve the performance of electronic devices (e.g., CMOS-based logic technologies [2] ). In recent years, however, strain-engineering paradigms have begun to shift, leading to the development of new devices, capable of generating a dynamic modulation of the mechanical deformations induced in the active materials (and, thus, of their optoelectronic properties).Micro-and nano-electromechanical systems (MEMS and NEMS), for example, have long been used for sensing applications, thanks to their ability to transduce external stresses (e.g., applied pressure/weights, molecule adsorption,...) into electrical signals. In the opposite regime they are, at least in principle, 2D materials, such as graphene, hexagonal boron nitride (hBN), and transition-metal dichalcogenides (TMDs), are intrinsically flexible, can withstand very large strains (>10% lattice deformations), and their optoelectronic properties display a clear and distinctive response to an applied stress. As such, they are uniquely positioned both for the investigation of the effects of mechanical deformations on solid-state systems and for the exploitation of these effects in innovative devices. For example, 2D materials can be easily employed to transduce nanometric mechanical deformations into, e.g., clearly detectable electrical signals, thus enabling the fabrication of high-performance sensors; just as easily, however, external stresses can be used as a "knob" to dynamically control the properties of 2D materials, thereby leading to the realization of strain-tuneable, fully reconfigurable devices. Here, the main methods are reviewed to induce and characterize, at the nm level, mechanical deformations in 2D materials. After presenting the latest results concerning the mechanical, elastic, and adhesive properties of these unique systems, one of their most promising applications is briefly discussed: the realization of nano-electromechanical systems based on vibrating 2D membranes, potentially capable of operating at high frequencies (>100 MHz) and over a large dynamic range.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/admi.202102220.