The biopharmaceutical industry is making strides each day, whether by investing in new therapies or reinventing existing ones, intending to treat patients safely and effectively. The investment in research and development in the biopharmaceutical industry runs into hundreds of billions of dollars globally. Some molecules start in the lab; however, they cannot make it through drug development to the end-user if a positive benefit-to-risk balance cannot be demonstrated in the intent-to-treat population. Regulatory authorities around the world maintain a close watch on these drug development activities and approvals, and beyond, by establishing mandated submission requirements that are highly regulated and governed by guidelines. This article provides medical writers new to regulatory affairs with a comprehensive overview of mandated safety submissions across the drug development lifecycle. These submissions range from single-case reports to aggregate reports, encompassing information from individual patient data to aggregated summaries over time. The article explains submission types, their regulatory basis (ICH and GVP frameworks), periodicity requirements, and practical considerations for documentation preparation across clinical development and post-marketing phases.