The Lattice Light Sheet Microscope (LLSM) is capable of imaging biological systems spanning four orders of magnitude in space and time. The system generates an optical lattice to create an ultra-thin light sheet to image biological samples over long periods of time and with very fine resolution. This allows for 4D living cell imaging, where experiments limited to seconds or minutes on other imaging platforms can be extended to hours. LLSM uses ultra-thin sheets of light to image 3D cellular dynamics for hundreds of volumes at dozens of frames per second at diffraction-limited resolution. An extremely sensitive primary objective coupled with a custom- designed illumination system allows optical sectioning using extremely low photon doses for imaging with unprecedented duration.