Harvesting ambient mechanical energy at the nanometer scale holds great promises for powering small electronics and achieving self-powered electronic devices. The self-powering capability allows electronic device packages to exclude bulky energy storage components and makes possible forgoing the inclusion of bulky battery components. Recent development of nanogenerators (NGs) has demonstrated a possible solution for the design of self-sufficient power source that directly draws energy from ambient mechanical resources. Piezoelectric nanowires (NWs) are the building blocks of NGs. In this review paper, theoretical calculations and experimental characterization methods for predicting or determining the piezoelectric potential output of NWs are reviewed first. Representative models of NGs are then discussed for harvesting mechanical energy from high-frequency acoustic waves and low-frequency vibrations/frictions. A numerical calculation is also presented to estimate the energy output from NW-based NGs. A potential practical application of NGs for harvesting energy from respiration is shown using piezoelectric polymer thin films. At the end, perspectives of the NG concept are discussed. The nanometer-scale piezoelectric and mechanical properties, the piezotronic effect, and large-scale manufacturing capability are suggested to be the essential aspects that would eventually lead the promising NG concept to a practical power source.