Metals and alloys with nanoscale structural features (such as grain size or twin thickness <100 nm) exhibit exceptional strength and unusual deformation mechanisms. But, the suppressed dislocation slip, grain-boundary instability, and limited strain hardening in these nanostructured metals can be detrimental to fatigue and fracture properties. In this article, recent advances in understanding the structural origins of fatigue and fracture resistance of nanocrystalline and nanotwinned metals and alloys are reviewed. Based on this understanding, microstructural engineering strategies, such as gradient grain size, controlled boundary mobility, or hierarchical nanotwins, alter the deformation modes and provide promising paths to develop nanostructured materials with improved fatigue and fracture properties.