Mechanical ventilation in critically ill patients must effectively unload inspiratory muscles and provide safe ventilation (ie, enhancing gas exchange, protect the lungs and the diaphragm). To do that, the ventilator should be in synchrony with patient's respiratory rhythm. The complexity of such interplay leads to several concerning issues that clinicians should be able to recognize. Asynchrony between the patient and the ventilator may induce several deleterious effects that require a proper physiological understanding to recognize and manage them. Different tools have been developed and proposed beyond the careful analysis of the ventilator waveforms to help clinicians in the decision-making process. Moreover, appropriate handling of asynchrony requires clinical skills, physiological knowledge, and suitable medication management. New technologies and devices are changing our daily practice, from automated real-time recognition of asynchronies and their distribution during mechanical ventilation, to smart alarms and artificial intelligence algorithms based on physiological big data and personalized medicine. Our goal as clinicians is to provide care of patients based on the most accurate and current knowledge, and to incorporate new technological methods to facilitate and improve the care of the critically ill.