Traditional antidepressants can take weeks to work. Rapid-Acting Antidepressants focus on treatments that relieve core symptoms within hours to days—especially vital for acute suicidality and severe functional impairment. We map the evolving science of glutamatergic modulation (NMDA receptor antagonism, AMPA throughput), neuroplasticity cascades (BDNF, synaptogenesis), and network-level effects visible on neuroimaging. The session compares administration routes and settings—IV infusions, intranasal therapies, monitored oral agents—and clarifies indications, contraindications, and patient selection, including medical and psychiatric comorbidities. We’ll cover protocol elements that matter: pretreatment screening (cardiovascular, substance use, mania risk), informed consent and expectations, dose titration, real-time monitoring of dissociation/blood pressure, and post-dose observation with safe transport. Maintenance strategies are addressed too: scheduling of repeat sessions, consolidation with evidence-based psychotherapy, and transition plans back to standard antidepressants or augmentation. Safety is foregrounded—managing transient dissociation, nausea, hemodynamic changes, misuse risk, and interactions with sedatives or stimulants—along with clinic operations (credentialing, crash-cart readiness, documentation standards). Measurement-based follow-up is essential: track suicidality, anhedonia, and function at 24–72 hours and weekly thereafter; embed relapse-prevention plans that include sleep, circadian regularity, and substance use screening. Equity considerations include cost, geographic access, and stigma; we discuss care models that partner with community clinics and tele-psychiatry for triage and continuity. By uniting mechanisms, protocols, and systems design, Rapid-Acting Antidepressants, search discoverability via rapid-acting antidepressant conference, and adjacent practice like treatment-resistant depression can shorten suffering safely and responsibly.