Direct electrochemical CO2 reduction is an important option for closing the carbon cycle by converting waste CO2 into valuable products. For this process, metal-based catalysts, carbon-based catalysts, and especially nanostructured catalysts have received much focus for their promising catalytic performance – yielding useful carbon-based chemicals and fuels, such as carbon monoxide, hydrocarbons, and alcohols. Significant advancements have been achieved in the past few decades due to improvements in catalyst design at the nanoscale. Rational nanoscale electrocatalysts have been achieved with tunable reactivity through the development of novel synthesis strategies, characterization techniques, and catalytic monitoring methods. This chapter provides a state-of-the-art descriptor framework to understand the reaction from first principles and basic knowledge of how nanostructured catalysts can be used for electrochemical CO2 reduction. The mechanisms of the various types of nanocatalysts, as well as control of intrinsic and extrinsic reactivity, are discussed. While examining the control of reactivity for these catalysts, this chapter provides in-depth knowledge of active site electronic structures, exposed interfacial area, and alloy catalyst systems for nanostructured CO2 reduction catalysts.