Medicines provide therapeutic benefits but also cause harm due to inappropriate use and adverse drug reactions (ADRs). ADRs may cause serious health consequences, imposing a significant burden on healthcare systems. Ensuring patient safety by minimising risk requires optimal ADR monitoring, transparency, accountability, and adherence to ethical principles throughout the stages of drug research and development, the approval process, and use in the real world. The current systems for assessing and assuring medicine safety have certain weaknesses and challenges, thereby increasing the risk that ADRs go unrecognised. This commentary, therefore, delves into the issues surrounding medicine safety, the risks entailed, challenges in detecting ADRs and potential solutions to address these issues. It is hoped that this piece will help stakeholders, including regulatory agencies, improve accountable systems, enhance patient safety, and foster public trust in medicines, thereby improving both individual and public health.