JACC Editor-in-Chief Harlan M. Krumholz, MD, SM, introduces the October 21, 2025 issue of JACC, which is devoted entirely to Dr. Milton Packer's adipokine hypothesis.  Dr. Krumholz explains the rationale behind dedicating the issue to this bold conceptual framework, which proposes that dysfunctional visceral fat and its secreted adipokines drive HFpEF. We're also thrilled to present readers with 10 accompanying expert commentaries that explore, challenge, and contextualize the hypothesis.