The purpose of this study was to pilot a telephonically delivered cognitive-behavioral therapy to treat moderate to severe depression in patients from rural primary care settings where specialized mental health care is scarce. The goal was to obtain preliminary evidence of safety and efficacy. Depression is treated principally in primary care, however the outcomes are poor. Outcomes for depression in rural primary care settings are worse than in urban settings in part due to lack of access to specialized mental health care. This study examined the potential utility and safety of telephone-administered Cognitive-Behavior Therapy (T-CBT) for the treatment of depression in a rural primary care setting. Eight patients from a rural primary care clinic with significant depression were enrolled in 8 weeks of T-CBT administered by trained psychologists. Patients showed significant improvements in diagnostic status, as well as reductions in depression based the Beck Depression Inventory-II and the Hamilton Rating Scale for Depression, and there were no adverse events or problems with patient safety.