Pharmacovigilance, the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems, has become increasingly critical in modern healthcare systems. In Uganda, as access to medicines expands and new therapeutic interventions are introduced, the importance of robust pharmacovigilance systems has never been more pronounced. This comprehensive review examines the current state of pharmacovigilance in Uganda, identifies key challenges and opportunities, and provides evidence-based recommendations for strengthening national pharmacovigilance systems. A systematic review of literature from multiple databases including PubMed, and Google Scholar was conducted, focusing on pharmacovigilance practices, adverse drug reaction reporting, and drug safety monitoring in Uganda from 2015 to 2025. Uganda has established national pharmacovigilance infrastructure including a National Pharmacovigilance Centre and electronic reporting systems. However, significant challenges persist, including low spontaneous reporting rates, delayed international visibility of adverse drug reactions, and substantial knowledge gaps among healthcare workers. Modern digital approaches, including mobile applications and community-based interventions, show promise for improving system performance. The rising importance of pharmacovigilance in Uganda requires a multipronged strategy combining digital tools, active surveillance, capacity building, and enhanced patient engagement to ensure optimal medicine safety and public health protection.