The synthesis of peptidomimetics is an area of research that has gained a lot of attention in recent years. Peptidomimetics are compounds designed to mimic the natural peptide but retain its activity with increased stability and bioavailibility, as a result of the structural changes introduced into the parent molecule. The most frequent of these changes are peptide bond surrogates, which contribute to the hydrolytic resistance of peptidomimetics. 1,2,4- and 1,3,4- oxadiazoles are commonly employed as bioisosteric replacements of the amide bond thus constituting these heterocycles as an important structural motif for the pharmaceutical industry. The article will therefore provide an insight into the synthetic methodologies leading to 1,2,4- and 1,3,4-oxadiazole formation to give the reader an appreciation of the field. This review covers all recent developments achieved in the classical synthesis. Additionally, it focuses on the emerging methodologies of microwave-assisted and solid phase synthesis, thus revealing the scope of influence that these methodologies have in the synthesis of 1,2,4- and 1,3,4- oxadiazoles.