Parent-Child Interaction Therapy (PCIT) is an intensive parent support program for caregivers and their children who exhibit difficult-to-manage disruptive behaviors. After more than four decades of research supporting its efficacy for reducing children's disruptive behaviors and improving parent-child relationships, PCIT has become one of the most popular and widely disseminated parenting support programs in the world. The evidence for the efficacy of PCIT can be found in many reviews of randomized clinical trials and other rigorous studies. To add to those reviews, our aim was to provide practical guidance on how PCIT can be part of an evidence-based program for families that depends on practitioner expertise, as well as attention to families' diverse needs. To do this, we describe the evolution of PCIT as practiced in a university-community partnership that has continued for over 20 years, alongside a narrative description of selected and recent findings on PCIT and its use in specific client presentations across four themes. These themes include studies of 1) whether the standard manualized form of PCIT is efficacious across a selection of diverse family situations and child diagnoses, 2) the mechanisms of change that explain why some parents and some children might benefit more or less from PCIT, 3) whether treatment content modifications make PCIT more feasible to implement or acceptable to some families, at the same time as achieving the same or better outcomes, and 4) whether PCIT with structural modifications to the delivery, such as online or intensive delivery, yields similar outcomes as standard PCIT. Finally, we discuss how these directions in research have influenced research and practice, and end with a summary of how the growing attention on parent and child emotion regulation and parents' responses to (and coaching of) their children's emotions has become important to PCIT theory and our practice.