The recognition that adverse childhood experiences have long-term negative effects parallels the explosion of evidence demonstrating how early experience gets into the body and brain. This knowledge, in turn, has significant implications for treatment of emotional and behavioral problems in early childhood. In this article, I offer a guide to practical application of this science, giving clinicians tools to support and build buffering relationships starting in the newborn period, with the aim of preventing toxic stress. I review four basic principles, address the implications for diagnosis, and apply these principles in the clinical situation.