Non-linear optical (NLO) crystals are widely used in advanced photonic technologies for second harmonic and difference frequency generation (SHG, DFG), producing coherent light at frequencies where existing lasers are unavailable. Isotropic glasses do not exhibit SHG or DFG, except temporary induced anisotropy under external stimuli, however, recent reports on glasses with chiral structural motifs and our preliminary work on hybrid glassy chalcogenides containing non-centrosymmetric HgI2 molecules show promising intrinsic NLO properties. Unlimited ability of glasses to be modified with corresponding change in the glass composition, structure and properties, and the possibility to prepare fibers or thin film waveguides open new perspectives for understanding the fundamental origin of NLO phenomena in isotropic media, and synthesizing new materials with superior NLO properties.