Available methods for screening for Down syndrome (DS) in twin gestations include maternal age, first-trimester nuchal translucency, first-trimester combined screening, second-trimester genetic sonography, second-trimester quad screening, and combinations of tests across different gestational ages. Biochemical screening is generally associated with detection rates at least 15% less than in singleton pregnancies. Nuchal translucency measurement may help close that gap, but the best available data (based on modeling) show approximately 75% to 85% detection rates for DS, with a 5% false-positive rate. Patients accepting screening should be aware of all options should a diagnosis of fetal aneuploidy be confirmed, including pregnancy continuation, termination of the entire pregnancy, and selective termination of an aneuploid fetus.