Using clinical trials, researchers have demonstrated effective methods for treating depression in primary care, but improvements based on these trials are not being implemented. This might be because these improvements require more systematic organizational changes than can be made by individual physicians. We interviewed 82 physicians and administrative leaders of 41 medical groups to learn what is preventing those organizational changes. The identified barriers to improving care included external contextual problems (reimbursement, scarce resources, and access to/communication with specialty mental health), individual attitudes (physician and patient resistance), and internal care process barriers (organizational and condition complexity, difficulty standardizing and measuring care). Although many of these barriers are challenging, we can overcome them by setting clear priorities for change and allocating adequate resources. We must improve primary care of depression if we are to reduce its enormous adverse social and economic impacts.