Pharmacovigilance is critical in ensuring drug safety and efficacy by detecting, assessing, understanding, and preventing adverse drug reactions (ADRs). This review provides a comprehensive analysis of pharmacovigilance, covering its historical evolution, current systems and regulations, methods and tools, the role of technology, and the challenges faced in the field. The historical background highlights key milestones and regulatory changes post-thalidomide disaster, while the section on systems and regulations discusses international and national frameworks such as those by WHO, FDA, and EMA. Methods and tools for pharmacovigilance, including spontaneous reporting systems, signal detection techniques, and risk management strategies, are examined. The role of advanced technologies like electronic health records (EHRs), artificial intelligence (AI), machine learning (ML), and social media in enhancing pharmacovigilance activities is explored. Challenges such as underreporting of ADRs, data quality issues, global harmonization, and resource constraints are discussed, along with potential solutions. By highlighting these aspects, the review underscores the importance of continuous improvement and global collaboration in pharmacovigilance to protect public health and ensure the safe and effective use of medicines.