Substance use disorders (SUDs) are chronic relapsing health conditions characterized by continued substance use despite negative consequences. Deaths arising from these disorders have reached epidemic levels in the United States – in 2023, 48.5 million people aged 12 or older met criteria for SUD in the past year.1 According to the National Survey on Drug Use and Health, in 2023, 5.3 million people misused prescription pain relievers, and 3.9 million people misused prescription stimulants.2 The potential for SUDs to occur is multifaceted – SUDs are products of genetic, biologic, and environmental influences. SUDs occur in individuals from all educational and socioeconomic backgrounds, and long-term vulnerability is mediated by a complex interplay of genes, environmental impacts, and biopsychosocial factors. Childhood trauma, mental illness, reduced access to resources, lack of opportunity, and social isolation can all raise one's susceptibility.3 On the other hand, access to education, employment, housing, substance use prevention and recovery support services, and mental health services can foster resilience and reduce risk. Research shows that some people who misuse prescription medications go on to develop a SUD.4 This can be curtailed through patient-centered care that includes comprehensive screening and shared decision-making prior to the first prescription being issued. Prior to prescribing medications with potential for misuse, guidelines5 recommend that practitioners use validated screening tools, many of which are freely available, to assess for potential risk factors. It is also recommended that practitioners combine information from screening tools with Prescription Drug Monitoring Program (PDMP) data and toxicology screening, as appropriate, to assess for concurrent substance use that might place patients at higher risk for use disorders or harms such as overdose.6 Practitioners should also provide specific counseling on increased risks for harm when prescribed medications are combined with other drugs or alcohol, as well as ensuring that patients have access to naloxone or other opioid overdose reversal medications and receive effective treatment for SUDs, if needed. Studies have demonstrated that SUDs have a hereditary component, with genetic risks accounting for 40-70% of vulnerability.7 Based on this, there is growing interest and research on genetic tests that may predict vulnerability to developing an SUD. Such tests represent a growing awareness of the potential for personalized medicine within the addiction space, with important questions arising about their role and use. 1