At the time when many nonlinear optical (NLO) materials for frequency conversion of laser sources in the mid and long-wave infrared have achieved their fundamental or technological limits, we propose heteroepitaxy as a solution to develop novel NLO materials. Heteroepitaxy, is the most applied method to combine two different materials—by growing one material on another. In this work we show that combining two binary materials in a ternary may significantly improve the NLO properties that are of great importance for the pursued applications. Plus, due to the closer lattice match to the related substrate, a ternary is always a more favorable heteroepitaxial case than the two completely different materials. We also discuss combining different growth methods—one close-to-equilibrium (e.g., hydride vapor phase epitaxy—HVPE) with one far-from-equilibrium (e.g., metal organic chemical vapor deposition (MOCVD) or molecular beam epitaxy (MBE)) growth processes—to explore new opportunities for the growth of novel heterostructures, including ternary layers with gradual change in composition. The combination of different materials by nature—organics with inorganics—in a hybrid quasi-phase matching (QPM) structure is another topic we briefly discuss, along with some innovative techniques for the fabrication of orientation-patterned (OP) templates, including such that are based on the most universal semiconductor material—Si. Still, the focus in this work is on a series of NLO materials—GaAs, GaP, ZnSe, GaSe, ZnTe, GaN… and some of their ternaries grown with high surface and crystalline quality on non-native substrates and on non-native OP templates using hydride vapor phase epitaxy (HVPE). The grown thick device quality QPM structures were used for further development of high power, compact, broadly tunable frequency conversion laser sources for the mid and longwave infrared with various applications in defense, security, industry, medicine and science.