The mechanical properties of ZnO nanowires are the “enabling factor” for piezotronic nanogenerators. Examining the size effects entail the determination of both elastic (i.e. the Young’s Modulus, E) and failure strength (e.g. fracture, fatigue, buckling, etc.) properties of ZnO nanostructures for nanogenerators. An investigation directed to both types of effects is presented here for the first time. On one hand the strength size effects are pointed out and discussed in the framework of a generalized Weibull framework that is set forward for ZnO NWs. On the other hand, the implications of the size effects on elasticity properties are discussed and quantified using numerical simulations. The results demonstrate that the stiffening of smaller NWs can adversely affect the performance in a non-negligible manner, suggesting that both mechanical size-effects have to be considered for design purposes.