Micro- and nanoelectromechanical systems have numerous applications in sensing and signal transduction. Many properties benefit from reducing the system size to the nanoscale, such as increased responsivity, enhanced tunability, lower power consumption, and higher spatial density. Two-dimensional (2D) materials represent the ultimate limit of thickness, offering unprecedented new capabilities due to their natural nanoscale dimensions, high stability, high mechanical strength, and easy electronic integration. Here, we review the primary design principles, properties, applications, opportunities, and challenges of 2D materials as the building blocks of NEMS (2D NEMS) with a focus on nanomechanical resonators. First, we review the techniques used to design, fabricate, and transduce the motion of 2D NEMS. Then, we describe the dynamic behavior of 2D NEMS including vibrational eigenmodes, frequency, nonlinear behavior, and dissipation. We highlight the crucial features of 2D NEMS that enhance or expand the functionalities found in conventional NEMS, such as high tunability and rich nonlinear dynamics. Next, we overview the demonstrated applications of 2D NEMS as sensors and actuators, comparing their performance metrics to those of commercial MEMS. Finally, we provide a perspective on the future directions of 2D NEMS, such as hybrid quantum systems, integration of active 2D layers into nanomechanical devices, and low-friction interfaces in micromachines.