Objective: To review the efficacy, safety, and role of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide for chronic weight management. Data Sources: A literature search of PubMed/MEDLINE and Google Scholar was performed using the search terms: semaglutide 2.4, weight, and obesity. Ongoing studies of semaglutide were identified utilizing clinicaltrials.gov. Study Selection and Data Extraction: All English-language articles evaluating the efficacy and safety of semaglutide 2.4 mg for weight management in humans were included. Data Synthesis: Once-weekly injectable semaglutide 2.4 mg is indicated as an adjunct to a reduced-calorie diet and increased exercise for chronic weight management in adults with a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with at least one weight-related comorbidity, such as hypertension, type 2 diabetes mellitus, or dyslipidemia. Semaglutide 2.4 mg has consistently demonstrated clinically significant weight loss across all phase 3 STEP (semaglutide treatment effect in people with obesity) trials, and long-term efficacy and safety have been confirmed for up to 2 years. Gastrointestinal side effects were the most frequently reported side effects, including nausea, vomiting, constipation, and diarrhea. Safety data for semaglutide 2.4 mg were consistent with that reported previously for the GLP-1 receptor agonist class. Conclusions: Semaglutide 2.4 mg is a highly efficacious agent for weight management, with a safety profile similar to that of other GLP-1 receptor agonists. It is a feasible option for chronic weight management, with data for up to 2 years. It is currently the only once-weekly weight loss medication, although cost may limit its utilization.