This review article aims to bridge the knowledge gap in providing comprehensive care to adults with Down syndrome (DS) in primary care settings. Despite the increasing prevalence of adults with DS, there is a significant lack of familiarity and comprehensive guidelines for their health care among primary care physicians. This often results in subpar health promotion, preventive screenings, and individualized care. This article attempts to provide guidance for healthcare providers on previsit preparation, clinic visit characteristics, testing and screening considerations, and decision making/guardianship for adults with DS. By emphasizing a patient-centered approach, this review aims to enhance the quality of care, reduce associated morbidity and mortality, and ultimately improve the health outcomes of adults with DS.