Interactions between advanced catalytic systems with ultra-low PGM (platinum group metal) loadings and various carbon supports have been investigated in order to harvest maximal catalytic performance without sacrifice in durability. Different classes of catalysts with controlled size, shape, surface morphology, composition and compositional gradients in the form of solid monometallic and multimetalic nanoparticles (NPSs), core-shell nanostructures and subsurface interlayers (CS), multimetallic nanowires (NWs), mesostructured thin film catalysts (MSTF) and multimetallic nanoframes (NFs) were evaluated at atomic level in conjunction with tailored carbon supports such as amorphous high surface area glassy carbon, carbon nanotubes (single and multiwall), carbon nanofoam, graphite, fullerenes and graphene. Activity and durability performance of the advanced classes of catalysts have been evaluated by rotating-disk electrode, membrane-electrode assemblies and various methods for structural characterization. Tailoring the properties of catalyst-support can lead to substantial increase of the electrode lifetime and superior fuel cell performance.