Down syndrome, or trisomy 21, is the most common chromosomal anomaly and is characterized by intellectual disability and a typical facies. People with Down syndrome can have abnormalities of multiple organ systems. Cardiac and respiratory system involvement is the most common cause of morbidity and mortality, although every organ system can be affected. Patients may present prenatally with findings on screening sonography. If the diagnosis is not made prenatally, it is apparent at birth because of the characteristic facial features and musculoskeletal findings. Children with Down syndrome present to the radiology department at various ages depending on the severity of the specific finding. The purpose of this paper is to review the most common antenatal and postnatal imaging findings of Down syndrome as they manifest throughout the body.