Closing the gap from bench to bedside demands evidence of target engagement, dose–exposure–response clarity, and endpoints that reflect lived recovery. Translational Psychopharmacology assembles the toolkit: receptor pharmacology and circuit models, PK/PD modeling, imaging and fluid biomarkers, quantitative EEG, digital phenotyping, and adaptive trial designs. We trace a molecule’s journey: in vitro selectivity and off-target checks; in vivo pharmacology and safety; first-in-human dose finding with modeling of exposure and occupancy; and early proof-of-mechanism studies that verify the brain is actually being “touched.” We discuss how to choose biomarkers that matter—receptor occupancy via PET, pharmaco-fMRI for network effects, endocrine or inflammatory signatures—and when pragmatic, scalable proxies (pupillometry, speech/motor signals, wearable sleep) can guide dose refinement. Clinical translation hinges on the right patients at the right time: enrichment strategies based on baseline biology, symptom structure, or circuit signatures; rescue protocols for emergent risk; and combination logic that avoids antagonistic mechanisms. We compare fast-fail designs to traditional phases, show how Bayesian/adaptive methods cut waste, and outline how to build platform trials that test multiple agents against shared controls. Safety is continuous: QTc, seizure threshold, metabolic and hepatic panels, and interaction screens—especially in polypharmacy psychiatry. Implementation starts early: manufacturability, stability, and drug–device combinations (e.g., intranasal delivery) planned before pivotal phases. Finally, we connect evidence to practice: labeling that reflects real populations, pragmatic trials, and learning health systems that continue dose optimization post-approval. With this approach, Translational Psychopharmacology, the shared methods at a translational psychopharmacology conference, and decision anchors like target engagement biomarkers accelerate development and de-risk deployment.