This review discusses the application of quantum dots (QDs), gold nanoparticles (NPs), and molecular switches in optical nucleic-acid diagnostics. The size-dependent optical properties of nanoscale materials, as well as the ability to tailor both material and surface composition of NPs, create exciting new possibilities in nucleic-acid analyses. Similarly, molecular assemblies of nucleic acids that generate "on-off" responses at the single-molecule (or particle) level offer significant advantages in diagnostics. Areas of interest in this review include: 1) QDs and fluorescence-in-situ-hybridization, microarrays, fluorescence resonance energy transfer and signal enhancement; 2) gold or silver NPs and colorimetric detection, fluorescence quenching, chemiluminescence, and electrochemiluminescence; and, 3) advances in the design of molecular beacons, hairpin probes and other diagnostic nucleic-acid constructs. We provide brief perspectives on the potential application of lanthanide NPs as optical probes, and the potential of nucleic-acid diagnostics in living cells. (C) 2008 Elsevier Ltd. All rights reserved.