The aim of the Cochrane Collaboration is to help people make well-informed decisions about health care by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of health care interventions. This aim is as relevant now as it was 20 years ago, when the Cochrane Collaboration was established. Substantial progress has been made toward addressing challenges to achieving the Collaboration's aim. At the same time, a huge amount of work remains to be done. Current challenges include improving the quality of reviews, methodological challenges, meeting the needs of contributors and users and taking on new challenges while staying focused on the Collaboration's aim. Radical thinking and substantial change may be needed to identify and implement pragmatic strategies to ensure that reviews are up-to-date and informative. Methodological challenges include the development and application of better methods for addressing explanatory factors, incorporating non-randomized evidence and making comparisons across multiple interventions. Innovations in editorial processes and strategies to meet the needs of low- and middle-income countries and diverse users of Cochrane reviews are needed. Finally, although it is important to consider broadening the aims of the Collaboration to include types of questions other than the effects of interventions and types of products other than the Cochrane Library, we should not lose sight of the aim of the Cochrane Collaboration. Addressing that aim is still a major challenge that requires the collaboration of thousands of people around the world and continuing improvements in the methods used to achieve that aim.