The era of modem molecular biology took roots in the mid-20th century with the discovery of the structure and function of the molecule of heredity, DNA. In the last 50 years, the molecular era has evolved into the recombinant era and has made revolutionary contributions to all facets of both fundamental and clinical science. At present, cloning technologies exist that allow the isolation and identification of virtually any gene and its product from any living organism. The shift in application of molecular biology to modern diagnostics can probably be traced to the year 1975 when the first practical recombinant analysis, the Southern blot, was published. Molecular biologic technologies derived from and related to that relatively simple hybridization analysis have evolved into ever more sophisticated, rapid, and sensitive recombinant technologies, such as per and in situ hybridization. 61 Occurring almost simultaneously, advances in hybridoma technologies complemented the recombinant era and helped provide important new opportunities to assess quantitatively a myriad of antigenic determinants on an extraordinary range of immunogenic macromolecules. As the wealth of information provided by molecular diagnostics continues to accumulate, the challenge for the future is the development of more rapid, less expensive, and more broadly informative tests. To this end, the present molecular methodologies are still in evolution. One cogent approach is the development of multiplex capability, whereby multiple epitopes or DNA sequences can be simultaneously detected and quantitated. 32,100 By such approaches, whole batteries of microorganisms, cytokines, target genes, and so forth might be diagnosed in a single automated process. Furthermore, isothermal technologies, such as SDA, can be applied to a much simpler environment, while combinations of nonisotopic labels, quantitative amplification steps, and solid phase chemistry should dramatically improve already powerful molecular diagnostic technologies. Although the list of human disorders currently amenable to molecular diagnostic approaches is already large, classic clinical laboratory technologies still provide the lion’s share of diagnostic information. The ability to successfully package the methodologies of the modern molecular era will inevitably determine the breadth of the clinical applications of molecular diagnostics and the rate at which they becomes increasingly acceptable to clinicians. Although the molecular era has already brought and will continue to bring dramatic improvements in diagnosis and treatment evaluation, this technology also raises new ethical issues that society must be prepared to address meaningfully. For example, would an individual found to carry a colon cancer or breast cancer susceptibility gene be subjected to job discrimination from employers wishing to avoid future health liabilities. Similarly, if a fetus is prenatally diagnosed with a genetic or malignant disease for which there is no current cure, should it be aborted, and if not, why should prenatal screening test for untreatable diseases be performed at all? Clearly, the present and future success of molecular diagnostics mandates that such ethical issues are addressed in an open and public forum, well in advance of routinely implementing such tests.