Imagine that 5 years from now, underlying pathophysiologies are better identified before treatment is started and that biomarker and comparative personalized treatment trials enable clinicians to identify another 20% of patients in the first stage of treatment who are far more likely to respond to a glutamatergic intervention than to the selective serotonin reuptake inhibitor used in STAR*D level 1 or to agents that counteract interleukin inflammatory processes in the brain. Now, imagine that 60% of patients might be early remitters instead of less than 40%. The productivity jump would be appreciable—and productivity is only the tip of the business iceberg. The total annual cost of depression to U.S. employers alone is generally reported to be in the hundreds of billions of dollars (1, 2). So further imagine the impact once it became established, as is likely, that more successful treatment of millions of individuals with depression in workplace settings not only improves productivity but saves millions or billions of dollars for employers, insurers, and society, raises stock prices, and accomplishes all these benefits while treating one of the most disabling diseases in the world. Greater partnerships among business leaders, clinical translational investigators, and clinical delivery networks will be required to roll out such intervention programs on a large scale, but the payoff should be profound.