Gene-based molecular diagnostics is changing the practice of medicine and will continue to do so for the foreseeable future. The major underlying principle of these diagnostic tests is the use of specific nucleic acid sequences as surrogates; amplification of the surrogate markers enables the detection of pathogens or disease-related gene mutations. Gene targets can be amplified by target-, probe- or signal-based methods. Combined use of nucleic acid amplification and enzyme-linked immunosorbent assay with methods such as immuno-polymerase-chain reaction allows us to detect protein at femtogram (10(15) g) levels. A variety of choices are available for the detection of amplified amplicons with the fluorophore-linked nanoparticles as the most sensitive markers. The unique advantages of using covalently-linked nanoparticles include the detection of single molecules, the ability to enrich molecules of interest with unprecedented detection sensitivity (up to zeptogram levels, 10(21) g) and the flexibility of multiple functionalization. Automation appears to be the current trend for high-volume molecular testing of infectious diseases. Molecular profiling of various diseases using genomic or proteomic approaches opens up a molecule wonderland with promise and emergence of new molecular testing that will likely impact the practice of medicine to a greater degree in the future. The future of molecular-based testing and the journey toward personalized testing will be discussed.