The complex molecular structure and interesting activation mechanisms of naturally occurring enediynes have inspired the synthesis of a variety of simpler model systems to mimic their properties. While in most model compounds nucleophilic attack, isomerization or bioreduction are used to activate the unsaturated system for diradical cyclization, some attempts have been made to employ metal-ion coordination for this purpose. Significant enhancement of the thermal reactivity has been achieved by metal-ion induced conformational and electronic changes of suitably substituted enediynes, such as 1, 5, 6, 17 and 18. Enediyne activation by stoichiometric or catalytic formation of vinylidene complexes, such as 22, from terminal alkynes has also been investigated. This paper summarizes recent results pursuing the activation of enediyne diradical cyclization by metal ions.