Counseling regarding the options for aneuploidy risk assessment is complicated and requires thorough counseling with the patient. Second trimester serum risk assessment has been the gold standard because of widespread availability, low cost, and vast experience with counseling and performance. First trimester risk assessment is becoming more widely available and provides increased sensitivity for Down syndrome detection with a detection rate of approximately 87% (95% confidence interval: 84.0% to 89.4%), at a fixed false-positive rate of 5%. With the advent of first trimester techniques, controversy has arisen as there are advocates for the different recently available approaches. In this chapter, we outline the various options in a manner that will provide practical information for physicians offering such testing. Clearly, implementation of first trimester risk assessment requires special training and meticulous quality control standards for nuchal translucency and laboratory measurements, access to chorionic villus sampling, and also appropriate counseling regarding risk assessment options.