Improving the prediction of successful ventilator weaning and extubation is a goal that all Intensivists and perioperative physicians strive for. The successful wean and extubation of ventilated patients decreases hospital length of stay and associated costs, but more importantly it also reduces patient morbidity and mortality. This review evaluates traditional and novel indices used in the assessment for ventilatory wean readiness. Novel equipment such as the Bicore pulmonary monitor and the CO2 SMO Plus are now available on the market to assess and monitor ventilator weaning and may offer some value in this process. We also review the non-respiratory factors affecting weaning and the role of the bedside nurse and respiratory therapist. Resolution of the pulmonary compromise and an understanding of respiratory physiology, used in conjunction with monitored indices of weaning parameters in a consistent fashion will continue to improve our success rates of ventilator weaning and extubation.