Hepatic encephalopathy (HE) is a debilitating neurological condition associated with cirrhosis, characterized by cognitive impairment ranging from minimal to overt symptoms. It significantly impacts patients’ quality of life and substantially burdens healthcare systems. This review examines current prophylactic strategies for HE, focusing on established treatments, emerging therapies, and predictive tools to identify high-risk patients. Traditional treatments such as lactulose and rifaximin remain the cornerstone of HE management, effectively reducing ammonia levels and preventing recurrence. However, novel approaches like L-ornithine L-aspartate, albumin infusions, and antioxidants like resveratrol show promise in further improving outcomes by addressing underlying pathophysiological mechanisms, including systemic inflammation and gut dysbiosis. Developing predictive models, such as the AMMON-OHE score and clinical-genetic risk assessments, enhances the ability to tailor preventive interventions to individual patient profiles. These advancements are crucial in mitigating the incidence of overt HE, reducing hospital admissions, and improving patient survival rates. The future of HE management lies in personalized medicine, targeting specific inflammatory and metabolic pathways, with the potential integration of genetic manipulation. Continued research is essential to refine these strategies, ultimately aiming to improve the prognosis and quality of life for cirrhotic patients at risk of HE.