Patients with mental illness often have co-occurring substance abuse which increases the risk for developing cirrhosis, particularly with common etiologies such as hepatitis and alcoholic liver disease. As such, knowledge of how the disease may impact medication prescribing is important. Unfortunately, there is a paucity of data to guide medication prescribing in these patients. Product labeling information should be used in the clinical decision making process. Additionally, clinicians should consider the etiology of disease, adverse effect profile, and pharmacokinetic parameters including solubility, product formulation, protein binding, hydrophilicity, metabolism, bioavailability, extraction ratios, excretion route, and half-life. Thoughtful consideration should be given when prescribing potentially hepatotoxic medications, and those which may increase bleeding risk in patients with coagulopathy. It is essential to ensure every medication has an appropriate indication and carefully evaluate the need for each medication. Overall, more research is necessary to support clinical decision-making with outcomes based research in patients with chronic liver disease.