The evidence-based practice of clinical psychology may begin with a review of efficacy studies, but it cannot end there. It needs to translate these data to the patient who presents for treatment. The chapter begins with a discussion of the principles whereby a clinical psychologist can seek to match evidence-based treatments to a client’s clinical presentation.The chapter additionally reviews future developments in personalized medicine and methods that have the potential to improve the matching of treatments to presenting problems. The chapter also considers how session-to-session progress can be monitored to identify when a patient’s progress deviates (either positively or negatively) from an expected course.The concept of clinical significance is described, and practical illustrations are provided of how this can be used to monitor progress and ways of responding to clients who are on and off track are outlined. The discussion of why Routine Outcomes Monitoring systems work is demonstrated by illustrating implementation in routine clinical conversations.