We are becoming increasingly aware that the manner in which our skeleton ages is not uniform within and between populations. Pharmacological treatment options with the potential to combat age-related reductions in skeletal strength continue to become available on the market, notwithstanding our current inability to fully utilize these treatments by accounting for an individual's unique biomechanical needs. Revealing new molecular mechanisms that improve the targeted delivery of pharmaceuticals is important; however, this only addresses one part of the solution for differential age-related bone loss. To improve current treatment regimes, we must also consider specific biomechanical mechanisms that define how these molecular pathways ultimately impact whole bone fracture resistance. By improving our understanding of the relationship between molecular and biomechanical mechanisms, clinicians will be better equipped to take full advantage of the mounting pharmacological treatments available. Ultimately this will enable us to reduce fracture risk among the elderly more strategically, more effectively, and more economically. In this interest, the following review summarizes the biomechanical basis of current treatment strategies while defining how different biomechanical mechanisms lead to reduced fracture resistance. It is hoped that this may serve as a template for the identification of new targets for pharmacological treatments that will enable clinicians to personalize care so that fracture incidence may be globally reduced.