The design of piezoelectric energy harvesting systems can be exploited for the development of self-powered sensors, human-powered devices, and regenerative actuators, as well as the development of self-sustained systems with renewable resources. With the introduction of two-dimensional materials, it is possible to implement piezoelectric nanostructures to exploit environmental energies, taking advantage of their flexible mechanical structures. This chapter aims to study the relevant contribution that piezoelectric two-dimensional materials have in energy harvesting. Among the two-dimensional piezoelectric materials analyzed are phosphorene, MXenes, Janus structures, heterostructured materials, and transition metal dichalcogenides (TMDs). These materials are studied through their performance from a piezoelectric point of view. The performance achieved by two-dimensional piezoelectric materials is comparable to or even better than that achieved by bulk piezoelectric materials. Despite the advances achieved so far, many more materials, as well as structures for the implementation of energy harvesting devices or systems, will be proposed in this century, so this research topic will continue to be interesting for research groups around the world.