Pain assessment of the child and adolescent with sickle cell disease is complex and challenging. We present a paradigm of pain assessment during a vaso-occlusive crisis in children and adolescents based on the Pain Assessment as a Social Transaction model. Using this model, the assessment of pain severity in sickle cell disease is uniquely highlighted as comprising at least 4 key factors: the limitations of current pain assessment tools, the existence of acute pain of various origins and the emergence and coexistence of chronic pain, the prevalence of cognitive deficits, and the sociocultural dynamics in America. Improved tools for pain assessment and targeted practitioner education are warranted.