The international cooperation and harmonization of pharmaceutical regulations are the critical factors for the successful development and review of medicines to ensure their timely availability for patients. The past 25 years have witnessed major challenges in this area, but also significant changes, particularly in the 1990s with the advent of the ICH initiative between pharmaceutical companies and regulatory agencies in Japan, Europe, and the USA. I was privileged to be involved in this program and sat on several of the working parties that saw the reduction in animal requirements, resources, and time that resulted from more than 50 harmonized regulatory requirements. Subsequently, I was pleased to see many other countries and regions were given the opportunity to join and they have benefitted from this initiative. One of the keys to the future has to be the possibility of regional reviews for medicines to maximize the limited resources and expertise in the world rather than every country endeavoring to become a competent authority.Although less popular in pharmaceutical policy discussions, pharmaceutical regulation without active enforcement assures neither quality of health care nor of pharmaceutical products. Enforcement of regulations is a problem in many countries, in particular in low-income countries. Many problems in pharmaceutical sectors have their root in financial incentives in their manufacture, importation, supply, prescription, and sales. Sometimes these financial incentives become barriers to evidence-informed policy making, for example, generics of ARV drugs not being registered to protect the interests of the brand-name industry, or mono-component artemisinin medicines not being de-registered, despite the WHO advice to do so. In other cases, regulations are adopted, while enforcement is left behind (e.g., not monitoring the sales of banned pharmaceutical products in pharmacies). Voluntary guidelines and self-regulation, often selected as an acceptable compromise, are rarely effective on their own.