Since the inception of critical care medicine and artificial ventilation, literature and research on weaning has transformed daily patient care in intensive care units (ICU). As our knowledge of mechanical ventilation (MV) improved, so did the need to study patient-ventilator interactions and weaning predictors. Randomized trials have evaluated the use of protocol-based weaning (vs. usual care) to study the duration of MV in ICUs, different techniques to conduct spontaneous breathing trials (SBT), and strategies to eventually extubate a patient whose initial SBT failed. Despite considerable milestones in the management of multiple diseases contributing to reversible respiratory failure, in the application of early rehabilitative interventions to preserve muscle integrity, and in ventilator technology that mitigates against ventilator injury and dyssynchrony, major barriers to successful liberation from MV persist. This review provides a broad encompassing view of weaning classification, causes of weaning failure, and evidence behind weaning predictors and weaning modes.