Frontier optical-imaging modalities exemplified by the lattice light- sheet microscope invented by Eric Betzig sets new visualization standards for analyzing and understanding sub-cellular processes in the complex and dynamic three-dimensional environment of living-cells in isolation and within tissues of an organism. By using ultra-thin sheets of light to rapidly illuminate biological samples with extremely low photon doses, 3D experiments previously limited to seconds or minutes by photo bleaching or by photo-toxicity, can now be done at diffraction limited resolution and high-temporal precision with unprecedented duration of minutes or hours. We believe this ability to image with minimal perturbations is ideally suited to support hypothesis-generating research geared towards new discoveries. The talk will illustrate how we use lattice light-sheet microscopy to ‘see’ in three dimensions the intracellular delivery of RNAi and antisense oligonucleotides in cells maintained in tissue culture conditions and also will describe our most recent efforts using lattice light sheet microscopy with adaptive optics to link processes that mediate and regulate the movement of vesicular carriers throughout cells and the biogenesis of organelles in both, isolated cells maintained in tissue culture conditions and cells within tissues of a living zebrafish embryo