Resonant micro- and nanoelectromechanical systems (MEMS and NEMS) have demonstrated a number of recent scientific advancements, translating into a wide range of potential sensing applications, including force and displacement detection, scanning probe microscopy and resonant mass sensing of chemical and biological species. Within the biomolecular sensing arena, vibrational motion of the devices is altered by selective adsorption of analytes to locally functionalized nanoscale sites on the surface of MEMS/NEMS oscillator. The shift in the resonant frequency is directly related to the mass of the adsorbed analyte. Additionally, NEMS devices, made by lithographic techniques, can be formed in highly uniform arrays in a manner that can be readily integrated with motion transduction and microfluidic systems. In our work, experimentally measured shift in the first eigenfrequency was correlated to the amount of mass loading from the binding events and verified using theoretical constructs. Under ambient conditions where considerable damping occurs, immunospecific detection of single Escherichia coli O157:H7 cells is demonstrated by measuring the out of plane vibrational resonant mode using an optical deflection system with thermal noise as an excitation mechanism. Further sensitivity enhancement utilizing vacuum encapsulation in conjunction with piezoelectric actuation and tailoring of the cantilever dimensions is demonstrated by measuring mass loading of a nonpathogenic insect baculovirus, single APTS, HMDS and OTS monolayers. To highlight the lower detectable mass limit, surface machined NEMS oscillators with integrated circular Au contacts and sub attogram mass detection sensitivity are used for selective immobilization of dinitrophenyl poly(ethylene glycol) undecanthiol based molecules. Furthermore, experimental and theoretical elucidation of optical actuation of NEMS cantilevers at large distances from the clamped end will be presented. Using a modulated laser beam, focused onto the device layer in close proximity to the clamped end of a cantilever beam, we concentrate and guide the impinging thermal energy along the device layer. Cantilever beams coupled to chains of thermally isolated links were used to experimentally investigate energy transport mechanisms in nanostructures. The nature of the excitation was studied through steady-periodic axisymmetric thermal analysis by considering a multilayered structure heated using a modulated laser source. Optical excitation allows actuation of flexural and torsional vibrational modes of suspended nanostructures. Using this actuation method, we demonstrate the controlled capture, detection and release of submicrometer particles from the oscillator surface by the application of forces imparted by the in-plane motion of the resonator. Additionally optical excitation was used to measure binding events of single double-stranded deoxyribonucleic acid (dsDNA) molecules to localized gold nanodots near the free end of a NEMS oscillator. For studies of nonlinear fluid-structure interactions, on the one end of the spectrum, NEMS were integrated within fluidic channels, and on the other end of the spectrum fluidic channels were fabricated within the NEMS structures. Lastly, dissipation mechanisms leading to quality factors in the range of 106 to 107 in ultra-thin perforated membranes will be discussed.