In this chapter, we highlight recent advances and perspectives in the design and synthesis of NLO-active metal-organic frameworks (MOFs). Some of these compounds show impressive second harmonic generation (SHG) responses and may have potential use in NLO-applications. Noncentrosymmetric MOFs can be synthesized mainly by using chiral ligands, unsymmetrical achiral ligands, and mixed metal ions. Organic ligands containing donor-π-acceptor systems can be incorporated into MOFs to improve the SHG activity of the bulk materials through push-pull effect. Some diamondoid or octupolar MOFs have been shown to exhibit excellent SHG properties. Besides, a number of MOFs with 2D grid-type or 1D helical chain structures display good SHG activity. © 2014 Springer-Verlag Berlin Heidelberg.