Background <p>A 2017 systematic review and 2021 update identified 114 studies regarding gabapentinoid (gabapentin and pregabalin) misuse, dependence, or overdose.</p> Objective <p>We aimed to update previous systematic reviews and describe new insights regarding gabapentinoid misuse.</p> Methods <p>PubMed was searched from 1 September, 2020 to 24 January, 2025 using the following four searches: “gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid AND” one of the following four substance misuse-related terms: “substance-related disorders [MeSH],” “overdose,” “abuse,” or “misuse.” Additional research was identified by reviewing papers cited by included studies. Studies presenting novel data regarding gabapentinoid misuse, dependence, or overdose were included. Non-English articles, review articles, and animal studies were excluded.</p> Results <p>One hundred studies (87 observational, 13 case reports/series) were included, from North America (33), Europe (39), Asia (20), Australia (7), and Africa (1). Sixteen studied gabapentin, 20 pregabalin, and 51 both medications. These studies corroborated previous findings that gabapentinoids are misused both for therapeutic and non-therapeutic purposes, often in conjunction with opioids or other substances, and commonly in people with substance use disorders and psychiatric conditions. Recent research built on the previous systematic review, providing more robust evidence that concomitant use with opioids or benzodiazepines increases overdose risks. New studies also highlight a growing body of evidence regarding misuse within the Middle East and North Africa, among adolescents, and in patients with chronic pain.</p> Conclusions <p>Newly published evidence demonstrated that gabapentinoid misuse remains a significant concern, including in several populations not often highlighted in previous research. It provides more compelling evidence that gabapentinoids increase overdose risk, particularly when used with opioids or benzodiazepines.</p>