In the US (as well as in many countries around the world), one out of six individuals will develop major depressive disorder (MDD) at least once in his or her lifetime. In addition to being highly prevalent, MDD is recurrent, can be lethal, and exerts staggering costs to society. In light of these facts, it is alarming that up to 50 percent of patients fail to respond to currently available pharmacological or psychological treatments, with even higher nonresponse rates (70 percent) in standard care. This workshop specifically focuses on addressing unmet needs in the field by inviting world-renowned experts working in disparate disciplines, levels of analyses, and species to explore the role of novel, non-monoaminergic mechanisms in the pathophysiology and manifestation of depression. Research in this area has attracted enormous interest in light of the potential to identify completely novel treatment mechanisms for MDD and stress-related disorders. Participants include: clinical neuroscientists, preclinical scientists, scientists investigating the genetic and epigenetic underpinnings of depression, molecular neuroscientists, computational scientists, basic neuroscientists, neuroengineers, clinical scientists, epidemiologists, social scientists, and biostatisticians. The vast majority of these experts have never worked together in the past, so the workshop provides a unique opportunity for cross-pollination of ideas and identification of areas for future collaborations.