Hospital acquired infections in critically ill patients are characterized by high incidence and poor prognosis, but the specific population may benefit from pharmacologic prophylaxis. For patients with ventilator-associated pneumonia, prophylaxis with systemic application or nebulized inhalation of antibiotics may be considered as a choice, depending on the characteristics of the patients and the time onset of the disease. For invasive aspergillosis (IA) in the department of critical care medicine, new perception is needed for its diagnosis and the need for prophylactic antifungal therapy should be evaluated for the high-risk group of IA. Reactivation of CMV is not uncommon in the department of critical care medicine, and prophylactic antiviral treatment may reduce the incidence of reactivation, but whether it improves clinical outcomes requires further exploration. When considering pharmacologic prophylaxis, it is necessary to conduct a thorough risk-benefit assessment of the target population, the type of drugs, and the mode of administration.