It is a frustrating situation for patient and clinician alike when healthcare recommendations from the clinician do not translate into real-time behavioral changes on the part of the patient. This can lead to burnout on the side of the clinician and distrust in the medical system on the side of the patient—all leading to poor health outcomes. This chapter aims to review situations that can contribute to patient disengagement and challenges in providing impactful medical care. We review the effects of poor communication, limited health literacy, the complexity of the healthcare system, and the social and cultural determinants of health. Consideration of these hurdles can help practitioners remain grounded in the reality of the challenges our patients face and help preserve our most empathic approaches. We also provide steps to identify when a patient may be primed to make changes. In those situations, it can be helpful to implement and utilize strategies like motivational interviewing to increase the potential for change.