Electrochemical energy storage solutions for long-duration use-cases should feature active materials with exceptional stability in their charged state. In this presentation, I will discuss how molecular engineering is a powerful toolbox for tailoring the properties of organic redox-active molecules used as active materials in redox-flow batteries, particularly long-term stability as a function of redox potential in electrolyte. Instability can come from a variety of fundamental physical phenomena in the flow cell: desolvation of charged active materials in the electrolyte over time, producing solids; disproportionation and other parasitic reactions, including those between actives and the electrolyte; degradation and fouling of polymer membranes in contact with highly oxidizing or highly reducing catholytes and anolytes, respectively. To manage these risks, I will offer potential solutions from the atomic to macromolecular scales in the active materials and polymer membranes, where there is vast opportunity to gain access to cell chemistries that meet target requirements for the technology. I will also offer a perspective on how to scale to meet cost targets set forth in the Long-Duration Energy Storage Grand Challenge and Technology Roadmap.