The current drug regulatory system is outdated and relies primarily on a process of premarketing evaluation, followed by periodic reviews of reported adverse events. While long-term medicine use for chronic conditions is now commonplace, current drug evaluation systems do not incorporate the comprehensive evidence accruing over time in clinical practice. Good quality, routinely collected data on medicines use are now available in some countries. Consistent with international opinion, we propose an expanded and integrated system of medicines regulation for Australia, based on a surveillance system that improves safety monitoring by complementing existing systems, making best use of routinely collected data, and leveraging the power of information technology. Australia is well placed to pilot such a model system.