Super-resolution spinning-disk confocal microscopy with optical photon reassignment (SoRa) is an advanced imaging technique that extends fluorescence microscopy resolution beyond the diffraction limit without the need for specialized sample preparation or intensive computational processing. By enhancing both lateral and axial resolution while preserving the rapid imaging speed of conventional spinning-disk systems, SoRa is particularly well suited for live-cell imaging and high-throughput studies. In contrast to other super-resolution approaches, SoRa enables fast, 3D imaging with low phototoxicity, making it ideal for capturing dynamic cellular events in real time. This chapter highlights the use of SoRa for two key applications: (1) high-throughput screening, specifically for assessing drug effects on neuronal processes such as dendritic outgrowth, and (2) high-resolution 3D imaging of live-cells including imaging mitochondrial trafficking in neurons. SoRa’s versatility, speed, and compatibility with standard dyes make it a powerful tool for a wide range of biological and drug discovery research.