Among other optical microscopy systems, the optical design and instrumentation behind single-molecule localization microscopy (SMLM) are relatively complex and calls for specialized skill. However, SMLM comes with the distinct ability to resolve features well beyond classical diffraction limit of \(\lambda /2\) , thereby cause a PArticle Resolution shift (PAR-shift) towards the single-molecule limit. Foremost, the techniques demand precision illumination and ultra-sensitive detection of the Stoke-shifted photons from activated molecules. The fact that molecules need to be prepared in a fluorescence state by light-induced photochemical reactions through the photoconversion process calls for additional light sources. This makes the microscope a dual-beam illumination system. In this chapter, we will discuss three different illumination schemes that are widely used in single-molecule localization microscopy: widefield, TIRF, and HILO. Most of the popular techniques (fPALM/PALM/STORM and variants) use one of these optical configurations for exciting the sample. In addition, recent progress in SMLM has seen the emergence of volume imaging techniques (3D STORM, fPALM-Biplane, SMILE, and scanSMLM) and a steady advance towards multicolor imaging, thereby facilitating the investigation of multiple proteins interactions. All these developments are possible with the emergence of single-photon sensitive detectors such as EMCCD, sCMOS, and SPAD. The final section of the chapter is dedicated to these sophisticated detectors and their working principle. The chapter is expected to give first-hand knowledge for the development of basic SMLM system.