Practice-based psychological intervention research that is conducted by practitioners in pediatric clinical settings raises special challenges that need to be met to maximize opportunity for success. Based on our experiences in intervention research conducted in clinical settings by practicing pediatric psychologists and health care providers, we consider issues in designing and implementing intervention research, resource development, interdisciplinary collaboration, ethical issues, data analysis, and application of findings in clinical practice. Recommendations to enhance the implementation of psychological intervention research in pediatric clinical settings include balancing feasibility versus validity in study design, considering multiple approaches to study designs and data analyses, identifying and managing ethical issues, facilitating interdisciplinary collaborations, developing resources, and enhancing opportunities for research training.