NOx selective catalytic reduction (SCR) with NH3 on Cu-zeolites is a commercial emissions control technology for diesel and lean-burn engines. Mitigating low-temperature emissions remains an outstanding challenge, motivating an improved understanding of the reaction mechanism, active site requirements, and rate-determining processes at low temperatures (<523 K). In this Perspective, we discuss how operando spectroscopy provides crucial information about how the structures, coordination environments, and oxidation states of Cu active sites depend on reaction conditions and sample composition; when combined with kinetic measurements, such operando data provide insights into the Cu site and spatial density requirements for reduction and oxidation steps relevant to the Cu(II)/Cu(I) SCR redox cycle. Isolated Cu ions coordinated to zeolite oxygen atoms ex situ become coordinated to NH3 in situ and dynamically interconvert between mononuclear and binuclear NH3-solvated Cu complexes to catalyze SCR turnovers. We conclude with future research directions that can benefit from combining quantitative kinetic measurements with operando spectroscopy.