Psychotherapy holds great promise for bringing about therapeutic change, yet a major challenge lies in translating short-term change into change that endures over extended time scales. This chapter tackles the “how-tos” of therapeutic change through the lens of an emerging field of research on internally guided experience, encapsulating thoughts and feelings. The authors first synthesize basic science and clinical research on functional and dysfunctional internal thought, highlighting the importance of alterations in content, processes and corresponding patterns of functional activity and connectivity of the brain’s default network. Next, they introduce a neurocognitive model highlighting spontaneous processes, deliberate processes, and automatic affective processes that promote and inhibit the dynamics of thought. They apply this dynamic framework to understanding mechanisms of change associated with common psychotherapies and review preliminary effects of therapy on brain activity and connectivity within and between large-scale brain networks. Throughout the chapter, the authors note many points of convergence with the integrated memory model, which inspired the edited volume to which this chapter belongs.