The diaphragm is the primary muscle involved in the ventilatory pump, making it a vital component in mechanical ventilation. Various factors in patients who require mechanical ventilation can lead to the deterioration of the diaphragm, which is associated with increased mortality. This deterioration can arise from either excessive or insufficient support due to improper adjustment of ventilation programming variables. It is essential for healthcare professionals to make appropriate adjustments to these variables to prevent myotrauma, which negatively impacts muscle structure and function. One recognized cause of muscle injury is eccentric work of the diaphragm, which occurs when muscle contractions continue after the expiratory valve has opened. Current evidence suggests that these eccentric contractions during mechanical ventilation can be harmful. This brief review highlights and analyzes the existing evidence and offers our clinical perspective on the importance of properly adjusting ventilation programming variables, as well as the potential negative effects of eccentric diaphragm contractions in routine clinical practice.