Developing technologies and methods are allowing practical access to single-molecule detection (SMD), manipulation, and analysis. New optical detectors and imaging devices permit rapid high-sensitivity and low-noise c apture of opt ical si gnatures f rom i ndividual mole cules. C hemically s elective opt ical labels such as uorophores or na noscale s cattering objects en hance t he opt ical sig nature of s elected molecules a nd ena ble t heir re cognition i n a c omplex m ixture. M icro-a nd na no uidic s ystems a re advancing technological capabilities that can couple optical analysis to small volumes of uid and also select and separate molecules of interest. Nanoscale structuring and optical methods combined with uid handling are being integrated into lab-on-a-chip tools for radically new approaches to analytical chemistry or biomole cular s tudy. ese to ols a re b eing d irected toward u ltrasensitive de tection a nd identi cation of molecules, even if rare in number or rate of occurrence. Future generations of DNA sequencing and gene e xpression may utilize single-molecule analysis (Eid et a l. 2009). SMD methods provide direct v isualization of mR NA dynamics w ithin live Escherichia coli c ells (Golding a nd C ox 2004; Golding et al. 2005), allowing access to study the rich biodiversity present within a given species of an animal or organism. is attention to biomolecule individuality and uniqueness enables studies and discoveries previously obscured in ensemble measurements.