From penicillin to insulin, from antiseptics to anesthesia and from X-rays to magnetic resonance imaging, science has led to dramatic improvements in health worldwide. With the sequencing of the human genome complete, science is on the verge of discovering remarkable new ways to diagnose, treat, prevent, and maybe even predict human diseases. Yet, all is not well. HIV/AIDS, malaria, dengue, and tuberculosis continue to wreak havoc, new foes like the SARS and avian flu viruses appear, and old scourges like polio remain recalcitrant enemies. Childhood infections and maternal mortality ravage the developing world, which also has to deal with increasing burdens of diabetes, obesity, and cardiovascular disease. Disparities and inequities in health remain major development challenges in the new millennium - and malfunctioning health systems are at the heart of the problem. Resource-poor countries struggle with creaking infrastructure, inadequate financing, migrating doctors and nurses, and lack of basic information on health indicators. Against a backdrop of history and a description of current global health challenges, Knowledge for Better Health takes stock of the state of global health research and reaches the following conclusions: 1. Health research must be managed more effectively if it is to contribute to strengthening health systems 2. Increased investments are needed in health policy and systems research 3. Public trust in science and scientists needs to be restored The Report provides a compass to reorient the health research endeavor to respond more effectively at national and global levels to contemporary public health challenges. This reorientation requires strengthening health research systems, creating an environment conducive to research-informed policy and practice, and focusing on key priorities in health policy and systems research. The Report's recommendations and action plan build on the past achievements of health research and highlight particular elements within health research systems that deserve special attention and closer management in order to make even more progress in the future.