This chapter uses a case study to explore communication and decision-making with parents and seriously ill children about phase 1 research trials. The chapter begins with a case scenario about 13 year-old “Gabby,” who has relapsed high-risk acute myeloid leukemia, which brings to the forefront ethical issues specific to communication and decision-making with parents and seriously ill children about phase 1 research trials. A brief history on phase 1 research trials in pediatric oncology is provided, followed by a review of the scientific literature regarding challenges to informed consent and child assent in this context. The chapter ends with evidence-based strategies for improving informed consent for pediatric phase 1 trials and questions for discussion.