Psychosocial issues in children, adolescents and families who suffer with chronic illnesses require careful identification and treatment. Since more of these young people survive into adulthood, their risk of psychosocial distress and psychiatric illness is increased, although many adapt well. The literature is vast, but limited in its usefulness: criteria for the variables described, including chronicity and severity, are poorly defined; outcome measures are not standardized; and few randomized controlled clinical trials exist. This chapter focuses the attention of physicians on overt and covert signs of psychosocial distress in the patient and family with chronic illness. Common issues for all chronic diseases are discussed and a non-categorical approach is taken. The importance of the family as a focus of intervention is highlighted. The meaning and treatment of unexplained medical symptoms, non- adherence with treatment recommendations, school refusal, sexuality and substance use and abuse are discussed.