In biochemical analyses, sample fluid volume in the nano or pico liter range is commonly encountered in various processes. For example, the preparation, mixing, separation, and concentration of cells and biomolecules in such small amount of fluids are very often needed in most analyses. From the science and technology point of view, efficient momentum and energy transfers of the desired fluid and particle motions in such small scales need sufficient comprehension of mechanics and MEMS (micro-electro-mechanical systems) transducers of similar length scales. Interestingly, MEMS/NEMS technologies do enable us to match the device and the fluid length scale for handling fluids in extremely small volume. This opens up a tremendous opportunity for research and development. In traditional fluid dynamics, the flow length scale is much larger than the molecular length scale. Continuum mechanics is the most common hypothesis used for flow research. In the case of micro/nano engineering systems, however, one may encounter regimes from continuum all the way down to molecule-dominated conditions. Therefore, in micro/nano fluidics, there are many new challenges that are very different from those in traditional fluidic systems. In this chapter, we discuss these special issues related to micro/nano fluidics and MEMS transducers in handling extremely small amount of fluids, including embedded particles.Keywords Micro-electro-mechanical-systems (MEMS), nano sciences and technologies, sensors and actuators, microfluidics and nanofluidics, micro/Nano systems et al., Microsystems and Nanotechnology