This article is intended as a brief review on the glucagon-like peptide-1 (GLP-1) agonist Semaglutide (Ozempic®, Rybelsus®, Wegovy®), an antidiabetic medication that has gained significant popularity in the United States for its role in long-term weight-loss management. While current research on GLP-1 agonists, including semaglutide, focuses primarily on their therapeutic effects in managing diabetes and obesity, information regarding their forensic and medicolegal significance is limited. Concerns related to GLP-1 agonists may arise due to their pharmacokinetics, potential drug-drug interactions, and side effects including hypoglycemia, which can be relevant in cases involving human performance, such as impaired driving, or in unexpected fatalities. Semaglutide additionally presents analytical challenges due to its large, highly charged molecular structure and potentially limited stability in whole blood, which may complicate its detection and quantification in forensic laboratories using common instrumentation. The development of robust analytical methods will be essential to account for its pharmacological effects and to address its potential role in intoxications or unexplained fatalities, especially in the context of misuse or off-label use for weight loss. A strong case can be made for the necessity of further research into the detection, quantification, and interpretation of semaglutide concentrations in forensic toxicology casework.