<p>Oxides are integral to heterogeneous catalysis, serving critical roles such as catalyst supports, active materials and electrodes. A highly ordered subset, single-crystalline oxides, have traditionally been used as model catalyst supports in fundamental surface science studies. However, advancements in bulk synthesis have rendered their general use more feasible for real-world applications. In this review, we explore the efficiency of single-crystalline oxides as active metals and supports across a wide range of heterogeneous processes, often performing exceptionally well. Beginning with synthetic methods, we discuss the advantages of single-crystalline oxides in thermo-, electro- and photocatalysis. Previously held conventions about catalytic activity, deactivation and surface–adsorbate interactions are re-evaluated by understanding how these ordered materials behave during the respective reactions. Last, we assess advances in characterization techniques and their impact on designing the next generation of catalysts based on single-crystalline oxides.</p><p></p>