Nitriles are organic compounds bearing the -C≡N functional group and thus derivatives of hydrocyanic acid. Besides their application in polymers, nitriles are also present in more than 30 pharmaceuticals, including antidepressants, antidiabetics, and anticancer drugs, since they can act as hydrogen acceptors, increase water solubility and shield the drug from oxidative metabolism. Moreover, nitrile derivatives are usually stable and inexpensive and can be converted into many functional groups and heterocycles, and, therefore, are very interesting precursors in the synthesis of robust molecular libraries in medicinal chemistry. It is also important to mention that 5- membered azaheterocycles are of the utmost importance in the medicinal chemistry field, being present in many marketed top-selling drugs. In this context, this chapter will provide an update on the synthesis of prominent 5-membered azaheterocycles from nitriles, focusing on the most interesting reactions and methodologies reported from 2014-2020.