In the past decades, numerous markers and strategies for Down syndrome screening have been developed. With the recent acceptance of first trimester and integrated screening as a part of routine clinical practice, there are now a variety of accepted screening protocols for Down syndrome. These choices can be confusing both to patients and clinicians. First trimester screening is at least as accurate as traditional second trimester screening and provides results earlier. Combining first and second trimester results increases the sensitivity and specificity of screening and reduces the number of women requiring invasive testing. However, the decision to screen and to perform invasive confirmative testing is a personal one that may be influenced by the presence or absence of a family history of aneuploidy or genetic disorders and by the woman's obstetrical and medical history, attitudes and beliefs about termination of pregnancy, education, religious beliefs, and economic concerns. The purpose of this article is to outline the various options in prenatal screening, and their individual advantages and disadvantages.