The Collaborative Care model is a systematic strategy for treating behavioral health conditions in primary care through the integration of care managers and psychiatric consultants. Several randomized controlled trials have demonstrated that Collaborative Care increases access to mental health care and is more effective and cost efficient than the current standard of care for treating common mental illnesses. Large healthcare systems and organizations have begun to adopt Collaborative Care initiatives and are seeing improved treatment outcomes and provider and patient satisfaction. This review discusses current research on the effectiveness and cost-efficiency of Collaborative Care. In addition, this paper discusses its ability to adapt to specific patient populations, such as geriatrics, students, substance use, and women with perinatal depression, as well as the significance of measurement-based care and mental health screening in achieving improved clinical outcomes. Current data suggests that Collaborative Care may significantly improve patient outcomes and time-to-treatment in all reviewed settings, and successfully adapts to special patient populations. Despite the high upfront implementation burden of launching a Collaborative Care model program, these costs are generally offset by long term healthcare savings.