Oxygen reduction catalyst activity and durability is critical to the success of polymer electrolyte fuel cells (PEFCs) as an energy conversion technology. Typically, rare and costly platinum-based materials are used as catalysts for the oxygen reduction reaction. Efficient utilization and preservation of the Pt catalyst surfaces must be achieved in order to reach the activity and stability required to manufacture cost-competitive products powered by PEFCs with long lifetimes. Our approach to meeting this goal employs atomic-level control of the positioning of active elements within the multimetallic catalyst. By understanding the segregation and migration of Pt within a bimetallic alloy, we are able to design advanced three-dimensional architectures such as the excavated, rhombic dodecahedral nanoframe. Careful control of catalyst synthesis and surface treatments yield surface composition profiles that balance high catalytic activity (~1.4 mA/cm² and ~0.6 A/mg_Pt at 0.95 V vs RHE) with the durability of the surface. We use atomic-level characterization such as ex situ TEM and in situ electrochemical ICP-MS to gain critical insight into the surface transformation during electrochemical cycling. These detailed studies are being combined with a synthetic scale-up effort to translate lab-scale (milligram) catalysts such as excavated nanoframes to the gram scale. The scale-up effort is critical to evaluating excavated nanoframes and other advanced architectures in a membrane electrode assembly (MEA), which is more likely to reflect real performance in the fuel cell stack. Ultimately, synthetic control and characterization at the atomic-level in combination with gram-scale catalyst synthesis provides the powerful ability to iteratively design advanced catalyst architectures that are thoroughly tested in both rotating disk electrochemistry and MEAs. These capabilities will yield new insight into low loading, high current density performance loss of MEAs, an enormous roadblock to the next level of major fuel cell commercialization.