The launch of the genomics and postgenomics era has greatly expanded our understanding of the genetic basis of many diseases. In conjunction with the sociocultural trend to delay childbirth and to maintain smaller family units, extra demand may be placed on the existing prenatal diagnostic services. The inherent risk of fetal loss associated with current prenatal diagnostic procedures, such as amniocentesis and chorionic villus sampling, has spurred research into non-invasive prenatal diagnosis. Much research has been conducted on the exploitation of fetal genetic material present in the maternal circulation. The initial focus was on the isolation of intact fetal cells and subsequently, the existence of extracellular fetal DNA in maternal plasma was realized. Exciting developments have been achieved in recent years. A large-scale trial to evaluate the clinical utility of fetal cell isolation from maternal blood for fetal aneuploidy diagnosis was launched and data were recently published. Much has taken place in the research of fetal DNA analysis in maternal plasma and in one example, namely prenatal RhD determination, this type of analysis has been used in the clinical setting. This paper reviews the technological developments in non-invasive prenatal diagnosis.