This brief account describes our progress on the regioselective synthesis of medium-sized heterocycles. Formation of the medium-ring (seven-, eight-, nine-membered) oxa-, aza-, thia, oxa-thia- and aza-thia-heterocycles has been achieved by the intramolecular metal-mediated cyclization (especially Pd-catalyzed), diene and enyne metathesis, thiol-mediated cyclization, iodocyclization and azide-alkyne cycloaddition.