This issue takes aim at some of medicine’s most perplexing issues. With organs for lifesaving transplants in short supply, some experts suggest rethinking what organs are suitable and who should get them. Parsing memory at the molecular level may help slow the decline of aging brains. And can personalized T cell therapy find a way to thwart the most deadly cancers? Plus tentative progress against a long misunderstood disease that leaves patients barely able to get out of bed.