In past decades, most individuals with Down syndrome were usually not afforded adequate medical care. Many children with Down syndrome were institutionalized and they were often deprived of all but the most elementary medical services. Fortunately, there have been major improvements in the health care provision during the past 20 years. Professionals who are providing services to persons with Down syndrome need to be aware of those clinical conditions that are more often observed in this population. Certain congenital anomalies (congenital cataracts, anomalies of the gastrointestinal tract, and congenital heart disease) often require immediate attention, as some of them may be life threatening. During the subsequent childhood years a number of clinical conditions and disorders such as infectious diseases, increased nutritional intake, periodontitis, seizure disorders, sleep apnea, visual impairment, audiologic deficits, thyroid dysfunction, and skeletal problems usually occur at a higher prevalence. During adolescence specific aspects of maturation and certain health issues (skin infections, thyroid disorders, increased weight gain, and others) as well as mental health concerns need to be taken into consideration. Similar concerns may also be observed during adulthood which in addition is often marked by accelerated aging and the threat of Alzheimer disease in some persons with Down syndrome. Special attention needs to be paid to these disorders and conditions during the lifetime of a person with Down syndrome. Appropriate medical care should be provided to and no form of treatment should be withheld from a person with Down syndrome that would be given unhesitatingly to an individual without this chromosome disorder.