This article reviews the growing body of work over the past decade investigating the effect of interface crystallographic character and resulting local interface structure on the mechanical behavior in bimetallic nanolayered composites. It has been shown that nanolayered composites exhibit enhanced strength, thermal stability, radiation damage tolerance, and resistance to shock deformation in comparison to their coarse-grained constituents. These unique behaviors are attributable to the high density of interfacial content, as well as the local interface structure and its influence on mechanically or irradiation-induced defects. Here, we cover recent literature on Cu-Nb nanolayered composites synthesized via different pathways including physical vapor deposition and severe plastic deformation techniques such as accumulative roll bonding. By altering the synthesis method, we can produce materials with similar chemical composition and layered morphology, while varying only the crystallographic character of the interface as defined by the orientation relationship and interface plane. This capability, in turn, opens an unprecedented opportunity for systematic investigation of the local interface structure on subsequent behavior, while keeping all other variables constant. We begin with a discussion of interface structures that develop as a function of their processing path. We then follow with the effects of interface structure on dislocation nucleation and deformation twinning. Next, we discuss interface effects on mechanical behavior at quasi-static ambient conditions and later under extreme strains, strain rates, and temperatures. Taken together, these examples provide a strong indication that interface structure matters. The exciting implication is that bimetal interfaces can potentially be engineered for optimal material performance.