One of the fastest growing immigrant groups in the United States is from the Indian subcontinent of South Asia. Included in this group are people from India, Sri Lanka, Bangladesh, and Pakistan. Although there is considerable heterogeneity within and between the populations of these countries, cultural similarities contribute to common challenges when South Asian immigrants are seen in primary care settings in the United States. This article describes aspects of the South Asian culture and of the acculturation process relevant to establishing rapport and providing competent biopsychosocial care to individuals and families from this region. We discuss the differing needs of recent immigrants, second-generation Americans from South Asia, and individuals temporarily in the United States for study or employment. We discuss linguistic and interpersonal style concerns in regard to the relationship between health care professionals and immigrant patients and use case material to illustrate cultural issues. We conclude with suggestions for culturally sensitive health care of South Asians.