We also highlight a beta-3 adrenergic receptor-involved mechanism that promotes stress resilience, through which antidepressant efficacy is achieved in both rodent models for depression and patients with major depression—an alternative therapeutic strategy that is conceptually different from the typical therapeutic approach in which treatment efficacy is achieved by reversing pathological alterations rather than by enhancing a good mechanism such as natural resilience. Here, ADRB3 is linked to depressive disorder.