Non-volatile oxide-based resistive RAM devices offer one promising route to continue Moore’s law and circumvent problems at small scales that have plagued traditional memory devices (DRAM, SRAM, and Flash). The RRAM ON and OFF resistance states are defined by the formation and destruction of a conductive vacancy filament in the oxide under applied bias. Given the complexity of this memory switching phenomena, first principle calculations can provide critical insight into the local electronic structure and defect formation and diffusion. I will discuss our recent work using different material combinations and dopants to optimize vacancy formation and diffusion in RRAM oxides (HfO<sub>2</sub>, Ta<sub>2</sub>O<sub>5</sub>). We examine a broad range of dopants from the periodic table and identify clear trends due to dopant valence charge and orbital character. I will also discuss how atomic disorder, electrode material and interface layers can affect vacancy dynamics, electronic transport, and device performance.