Much has changed in the 5 years since the responsibility for editing the JCI was transferred to Columbia University. Wars and a hurricane have conspired with other factors to overwhelm the national treasury. Support for investigator-initiated research at the NIH is now at a level that jeopardizes the nation’s ability to adequately train future scientists to maintain the country’s leadership in biomedical research. Indeed, there is insufficient support for even the best and brightest biomedical scientists to pursue the frontiers of the sciences at a time of unprecedented opportunities. Human embryonic stem cell research is still being suppressed in the United States. Economic models that enable academic health centers to flourish in the face of increasing challenges and the rising costs of health care have for the most part remained elusive. Translational research has become the buzzword, but there is widespread confusion and disagreement about how to do it. Despite all of these and other challenges to the biomedical research enterprise, the JCI remains vibrant, with record numbers of submissions and a loyal and enthusiastic readership.