The development of technologies towards the detection of mutations represents one of the most important areas of molecular biology. It has played a pivotal role in the tremendous success of the elucidation of complex biological problems, including genetic diseases. Today, these proven and emerging technologies have become the basis of successful biological investigations. More importantly, they are expected to play a central role in medicine, particularly the diagnosis and prognosis of genetic diseases including genetic predispositions, the assessment of treatments including transplants and decisions on reproductive choices. In addition, these technologies hold the key to future breakthroughs. This review provides an up-to-date examination of the principles of genetic diseases, the theories behind current methods of genetic diagnosis and detection of mutations including strategies for modification and the development of future technologies as they impact on the practice of medicine and on society as a whole.