This paper, the first in a series commissioned by NIMH for the "Challenges for the 21st Century: Mental Health Services Research Conference," seeks to provide a broad perspective on the primary care/mental health interface in the United States. The manuscript examines both the care of mental disorders in medical settings, and also the medical care of the seriously medically ill. The first section provides a historical overview of the cycling patterns of growth and retrenchment of primary care medicine during the 20th century, and the how those changes have paralleled the care of mental disorders and the mentally ill. The second section examines the four core features of primary care -first contact, longitudinality, comprehensiveness and coordination -and their implications for these issues. An historical and system-level perspective can provide a crucial step towards improving care on the mental health/primary care interface.