This article examines the evolving understanding of depression and the mechanisms behind ketamine’s antidepressant effects. It discusses the shift away from the traditional “chemical imbalance” theory toward a broader focus on neural connectivity, synaptic function, and brain plasticity. The authors explain how ketamine may rapidly restore communication pathways within the brain, offering a different therapeutic approach than conventional antidepressants. The paper also explores emerging research into multiscale plasticity and how these findings may influence the future of depression treatment and neuroscience.