Electrochemical systems, such as fuel cells, batteries, and water-splitting devices, represent the most efficient and environmentally friendly technologies for energy conversion and storage to date. Typical electrochemical reactions for energy use such as the oxygen reduction reaction (ORR) require efficient catalysts to reduce reaction over-potentials. Advances in chemical syntheses have led to the formation of various types of nanoparticles (NPs) with more rational control of size, shape, composition, structure and catalysis. This chapter will review our recent efforts in the development of Pt and non-Pt based NPs as advanced catalysts for electrochemical reactions including ORR, formic acid oxidation (FAOR), and selective CO₂ reduction. Various alloy and core–shell NPs with controlled electronic (alloying) and strain (geometric) effects for tuning electrocatalytic activity are systematically discussed. Guidance to rational design and synthesis of advanced electrocatalysts with much improved activity and performance durability for electrochemical energy applications is also addressed.