Treatment-Resistant Depression (TRD) is in a special class of depressive disorders that rarely respond to medications or therapy alone. When depression persists despite normal treatment, those suffering become disillusioned and may blame themselves for lack of a positive response. Suicidal ideation and substance use are all too common responses to such situations and complicate the lives of the affected. Combatting TRD requires multimodal treatment including medication augmentation strategies, neurostimulation, intensive psychotherapy, and behavioral activation (exercise, social activity, work, and volunteerism). Our affiliation with Houston Methodist Hospital’s psychiatry department allows for second opinions and rapid referral for neurostimulation services if deemed appropriate.