Children with severe neurological impairment are non-verbal, non-mobile and cognitively impaired. Pain is the most common symptom reported by parents, but when the child cannot tell us where it hurts, parents and health care providers rely on interpretation of non-specific behaviours to detect the presence of pain. The PIUO Pathway is a tool that ensures vulnerable children with unexplained pain are evaluated in a focused, efficient manner, addressing a vexing problem in specialist care of children with serious illness. We tested the PIUO Pathway as a clinical guideline in a multi-centre, randomized trial.  We will report on the Pathway, the study method, and emerging results from this recently completed study. This symposium will spark a conversation about different facets of developing and implementing a guideline for serving children with significant neurological impairment and unexplained pain and irritability within the objective of providing family centered care.