The need for implants to repair large bone defects is driving the development of porous synthetic scaffolds with the requisite mechanical strength and toughness in vivo. Recent developments in the use of design principles and novel fabrication technologies are paving the way to create synthetic scaffolds with promising potential for reconstituting bone in load-bearing sites. This article reviews the state of the art in the design and fabrication of bioactive glass and ceramic scaffolds that have improved mechanical properties for structural bone repair. Scaffolds with anisotropic and periodic structures can be prepared with compressive strengths comparable to human cortical bone (100–150 MPa), while scaffolds with an isotropic structure typically have strengths in the range of trabecular bone (2–12 MPa). However, the mechanical response of bioactive glass and ceramic scaffolds in multiple loading modes such as flexure and torsion — as well as their mechanical reliability, fracture toughness, and fatigue resistance — has received little attention. Inspired by the designs of natural materials such as cortical bone and nacre, glass-ceramic and inorganic/polymer composite scaffolds created with extrinsic toughening mechanisms are showing potential for both high strength and mechanical reliability. Future research should include improved designs that provide strong scaffolds with microstructures conducive to bone ingrowth, and evaluation of these scaffolds in large animal models for eventual translation into clinical applications.