Mechanical ventilation (MV) has been an essential tool in critical care for over seven decades, serving as a pivotal method in managing patients with respiratory failure. This chapter explores the fundamental principles, types, and indications of MV, providing a comprehensive overview of its applications in modern medicine. Additionally, it delves into the complexities of prolonged mechanical ventilation (PMV), addressing its definition, risk factors, complications, and outcomes. PMV patients represent a unique and challenging population, with a worse prognosis and significant economic impacts on healthcare systems. Addressing their needs requires a holistic perspective, taking into account each individual’s psychosocial context, aiming to alleviate suffering and promote happiness with the best possible quality of life. By examining the core principles of MV and focusing on the intricate needs of PMV patients, this chapter aims to equip healthcare professionals and students with the knowledge necessary to optimize patient care and outcomes in this critical area of practice.