Refractory out of hospital cardiac arrest is a common problem that is associated with poor overall survival rates and neurological outcomes. There are various definitions that have been used but the most accepted one is cardiac arrest that requires more than 10 minutes of Cardiopulmonary Resuscitation (CPR) efforts or more than 3 defibrillation attempts. There have been different pharmacologic and non-pharmacologic therapies that were studied in these patients. None of the antiarrhythmic or vasopressor medications have been consistently shown to improve survival or neurological outcomes in this subset of patients. This has led to the introduction of various devices aimed at improving outcomes such as mechanical CPR devices, Extracorporeal Cardiopulmonary Resuscitation (ECPR), targeted temperature management and early invasive approach. There is accumulating evidence that there seems to be an improvement in outcomes when these devices are used in refractory cardiac arrest patients. But none of these devices have been shown to improve outcomes when used in isolation. This underscores the importance of systematic approach to these complex patients and using these therapies in combination. There has been a paradigm shift in the approach to these patients. Instead of repeated and prolonged CPR attempts in the field, it is suggested that these patients need to be moved to cardiac arrest centers with a mechanical CPR device in place, so a percutaneous Extracorporeal Membrane Oxygenator (ECMO) can be placed to “buy” time for other therapies such as therapeutic hypothermia and early coronary angiography followed by intervention as indicated. Careful selection of patients who might potentially benefit from this approach is critical to the success of these programs.