Cyclobutenones, four‐membered ketones bearing an unsaturated carbon–carbon double bond, and their structural sibling benzocyclobutenones, possess unique reactivity. Owing to their inherent high ring strain, such structures readily undergo ring opening under a variety of conditions, including thermolysis, photolysis, and transition metal catalysis, to afford reactive intermediates that can be trapped with nucleophiles, dienophiles, and unsaturated bonds. Their electron‐deficient enone moieties are good electrophiles for facile nucleophilic addition. Such properties render cyclobutenones versatile synthons, serving as excellent coupling partners in a vast array of synthetically valuable transformations. Square routes: Cyclobutenones and their structural sibling benzocyclobutenones possess unique reactivity due to the ring strain and electron‐deficient enone moieties. Such properties render them serving as excellent coupling partners in a variety of synthetically valuable transformations.