Herein, we describe studies relevant to heterocyclic chemistry carried out with low-temperature matrix isolation technique in conjugation with infrared (IR) spectroscopy. These studies comprise structural characterizations, ultraviolet (UV) and thermal reactivity, IR-induced processes, and quantum tunneling reactions. Focus is given mainly to examples from recent investigations conducted in our group. Unprecedent mechanistic insights on reactions involving heterocyclic compounds that result from such studies are highlighted.