PURPOSE OF REVIEW: Despite advances in critical care medicine, the incidence of clinically important upper gastrointestinal bleeding (UGIB) remains consistent. One therapy that reduces UGIB is the use of stress ulcer prophylaxis (SUP). In the past year, several key manuscripts have been published regarding SUP, providing updated recommendations for its prescription. In this review, we provide commentary on these recommendations and areas for future research. RECENT FINDINGS: Risk factors for UGIB include chronic liver disease, coagulopathy, severe neurologic illness or injury, and shock. The prescription of SUP is associated with a decreased occurrence of UGIB but no benefit in mortality. Although both histamine-2 receptor antagonists and proton pump inhibitors (PPIs) are recommended for SUP, it is possible that PPIs may be associated with increased mortality in critically ill patients. The short-term use of SUP is not expected to be associated with most adverse drug events, but inappropriate continuation of SUP increases this risk. SUMMARY: Patient-specific considerations based on recent data help with improving the prescription of SUP, although additional research is necessary. The use of artificial intelligence may be able to predict at risk patients with the potential to influence appropriate prescription of SUP and reduce the occurrence of UGIB.