Background: COVID-19 infection, which appeared for the first time in December 2019 in China as a combination of severe respiratory symptoms among which is pneumonia. A very common and severe complication of COVID-19 severe illness is the respiratory failure or acute hypoxemic respiratory insufficiency. This complication requires ventilation therapies to supply adequate oxygen for the patient. The World health organization (WHO) recommends the performing of endotracheal intubation in hypoxemic respiratory failure patients with acute respiratory distress syndrome who continue to have breathing problems however they received standard therapy of oxygen. Objective: This study aimed to assess the challenges related to intubation and ventilation, when to start intubation and how to deal with different outcomes and problems related to them. Methods: These databases were searched for studies published between December 2015 and April 2022 that had been peer-reviewed and had been published in English in the two databases: PubMed and Google Scholar. More synonymous key words had been used for searching such as intubation and ventilation challenges, ICU, ARDS and COVID-19 patients. Documents written in a language other than English have been disregarded since no sources for interpretation were discovered. Dissertations, conversations, conference abstract papers, and anything other than the primary scientific investigations had been disqualified.   Conclusion: Early intubation is recommended over late intubation. The intensivist, ICU nurse, and respiratory therapist (RT) are crucial team members to manage intubation and ventilation. Prone positioning is an important aspect to be applied. Lung injury occurs often in serious COVID-19 patients due to the severe and protracted respiratory failure that occurs in these patients. Majority of PE patients experience some degree of hypoxia as a result of ventilation-perfusion mismatch and intrapulmonary shunting.