There is much debate over a precise definition of treatment-resistant depression (TRD) as well as the method of staging this illness. Although there is some non-consensus on a definition for TRD, the most widely accepted definition of TRD is a failure to achieve clinical improvement of depressive symptoms following a trial of two or more antidepressant medications from two or more different pharmacological classes at adequate dosage, duration, and compliance. Some sources lower the threshold to failure of one medication, but most support two medications. Although both men and women can be effected by TRD, our review found a slight predominance in older women. Here we present a 62-year-old female diagnosed with severe major depressive disorder that meets the criteria for treatment-resistant depression. This patient failed to experience consistent relief of symptoms using different antidepressant monotherapies as well as different combinations of therapies. Transcranial magnetic stimulation provided a brief relief of symptoms in this patient; however, relapse occurred a few months later. This case is unique as this patient has recently experienced significant relief of her depressive symptoms using amphetamine and dextroamphetamine (Adderall) as an adjunct to her antidepressant therapy. We will review the literature that currently exists on treatment-resistant depression and the treatment options for TRD, as well as present our case. To our knowledge, a case of TRD responding so strongly to Adderall after failing to respond to such drastic pharmacologic measures, as well as TMS, has not been reported.