Optical computational imaging seeks enhanced performance and new functionality by the joint design of illumination, optics, detectors, and reconstruction algorithms. In this talk we discuss how this approach helps overcome the diffraction limit in fluorescence microscopy. Abbe’s resolution limit has been overcome after more than 130 years enabling unprecedented opportunities for optical imaging at the nanoscale. Fluorescence imaging using photoactivatable or photoswitchable molecules within computational optical systems offers single molecule sensitivity within a wide field of view from far field measurements. The advent of three-dimensional point spread function engineering associated with optimal reconstruction algorithms provides a unique approach to further increase resolution in three dimensions. Compressive imaging techniques further enable resolution of dense emitters and enable acceleration of the super-resolution data collection.