Sepsis remains a significant healthcare challenge, with high mortality rates and substantial economic burden. Pharmacists play a crucial role in optimizing medication use in sepsis management, particularly in the emergency department (ED) setting. This review article aims to explore the various pharmacist-led initiatives that have been implemented to enhance medication management in sepsis within the ED. The interventions include medication reconciliation, antimicrobial stewardship, dose optimization, therapeutic drug monitoring, and patient education. By actively engaging in multidisciplinary teams, pharmacists can contribute to early recognition of sepsis, appropriate antibiotic selection, and timely administration of medications, ultimately improving patient outcomes. This review synthesizes current evidence on the impact of pharmacist-led interventions in sepsis management in the ED, highlighting their effectiveness in reducing mortality, length of stay, and healthcare costs. Furthermore, challenges and barriers to implementing these initiatives are discussed, along with potential strategies to overcome them. Overall, pharmacist-led initiatives are integral in optimizing medication use in sepsis management and should be further promoted and integrated into standard care practices in the ED.