Evidence-based clinical practice guidelines for treating depression in primary care settings were developed, in part, to ensure that health services are provided in a consistent, high-quality, and cost-effective manner. Yet for a variety of reasons, guideline-based primary care for depression remains the exception rather than the rule. This work provides a brief review of effective strategies used to customize and then deliver evidence-based treatment for depression in primary care settings; describes two representative case studies that illustrate locally customized collaborative care strategies for treatment delivery; and concludes with principles and implications for policy and practice based on our practical experiences.