Background: Depression is a common comorbid condition with multiple sclerosis (MS). Historically, however, it has been undertreated. Little is known about the characteristics of those who receive, or do not receive, treatment for depression in the MS population. This study evaluated depression treatment in patients with MS, associated patient characteristics, and probable determinants of antidepressant drug use in those with and without depression. Methods: A total of 152 patients with MS completed questionnaires and the Structured Clinical Interview for DSMIV- TR (SCID) to determine depression status. Tabular analyses and a binary regression model were used to identify patient characteristics associated with antidepressant drug use. Results: Of participants with major depression according to the SCID, 65% were taking antidepressant medications. With adjustment for successful treatment (antidepressant drug use by those not currently depressed and currently depressed), the prevalence of treated depression increased to 85.7%. Of those receiving treatment for depression, 19% were receiving nonpharmacologic treatment alone, 38% were taking antidepressant drugs only, and 44% were receiving both pharmacologic and nonpharmacologic treatments. Demographic and clinical variables were not statistically significantly associated with antidepressant drug use in those with depression. Conclusions: A large proportion of participants with depression in MS are now receiving treatment, a change from previous reports. The adequacy of treatment has become a bigger question because many of the treated patients continued to have depressive symptoms. Further research is needed to identify ways to achieve better outcomes for depression.