Screening for Down syndrome is an important part of routine antenatal care. The most common screening method in the United States involves the assessment of a combination of factors: maternal age, multiple second-trimester serum markers, and second-trimester ultrasonography (as a so-called "genetic sonogram"). More recently, however, there has been significant interest in first-trimester methods of screening, including screening for first-trimester serum markers and the sonographic measurement of fetal nuchal translucency. Multiple studies have demonstrated that fetal nuchal translucency has the potential of being a very powerful predictor of fetal aneuploidy. However, for clinicians a large void remains between this knowledge and the practical issues that must be addressed prior to endorsing this form of screening for widespread use. This article provides an objective assessment of the literature describing nuchal translucency, as well as some adjunct first-trimester sonographic techniques, such as ductus venosus flow and nasal bone studies. Additionally, a detailed description of practical problems that might limit the implementation of this form of screening is presented.