BACKGROUND: Hepatic encephalopathy (HE) is a common neurocognitive cirrhosis-related complication with a broad range of symptoms. Timely recognition and treatment of HE, including identifying precipitating factors, when possible, is critical for improving outcomes in patients with cirrhosis. Lactulose and rifaximin therapies, as appropriate, are recommended for patients with cirrhosis and a history of HE episode(s) to reduce risk of HE recurrence. OBJECTIVES: To provide clinical considerations for nurse practitioners and physician assistants (PAs) on the diagnosis and management of patients with cirrhosis. DATA SOURCES: A PubMed search of English-language articles published between January 1, 2008, and March 13, 2024, was performed to identify publications on the diagnosis and treatment of HE. RESULTS: Important topics to address when discussing care with patients with cirrhosis and their caregivers include concomitant medication use, recent infection history, comorbid conditions (e.g., diabetes), fall and frailty risks, and sleep quality. In addition, ensuring treatment adherence is important for reducing the risk of future HE episodes and HE-related hospitalizations. Engaging and empowering caregivers helps reinforce the need for patient adherence to treatment and facilitates earlier identification of HE symptoms. CONCLUSIONS: Early recognition of HE, treatment, and reduction in risk of recurrence are imperative to minimize patient morbidity and mortality. IMPLICATIONS FOR PRACTICE: Nurse practitioners and PAs play an important role in supporting patients with cirrhosis who are at risk for developing HE, as well as their caregivers. Understanding and recognizing precipitating factors and clinical symptoms of HE and treating and preventing HE recurrence can improve patient outcomes.