There is significant unmet need for new therapies for the treatment of depression. Only 29 active substances have been approved for major depression since 1959. Clinical trials initiations for new therapeutics in depression are down over 50% over the last decade. Despite the challenges, there are bright spots of innovation in major depressive disorder. This panel will discussion will explore examples of current innovative drug program that may be overcoming these obstacles and explore solutions to the unmet need in depression.