The treatment of un-dilatable coronary in-stent restenosis (ISR) lesions can be extremely challenging. Though there are various therapeutic approaches to this complex lesion subset, there is no consensus on one best treatment option and the path chosen often differs based upon the facility and operator preference. However, there is certainly consensus on this point: the best way to treat un-dilatable ISR is to prevent its occurrence. This situation most often arises due to poor lesion preparation during the original procedure. Proper technique with intravascular imaging and aggressive lesion preparation could significantly reduce or possibly prevent this problem from occurring. An ounce of prevention is worth a pound of cure.