Besides their biological activity, the importance of β-lactams as synthetic intermediates has been widely recognized in organic synthesis because ring cleavage of any of the four single bonds of the β-lactam system is enhanced by ring strain. Selective bond cleavage of the 2-azetidinone ring coupled with further interesting synthetic transformations renders these fascinating molecules powerful synthetic building blocks. Opening of the β-lactam ring can occur through cleavage of any of the single bonds of the four-membered ring. However, the sequential or simultaneous fragmentation of two bonds of the 2-azetidinone ring has been seldom reported. The present account is a survey of the recent salient synthetic achievements exploiting selective bond cleavage of the β-lactam nucleus, with particular emphasis to diastereoselective processes. The usefulness of these substrates for the preparation of substances of biological interest, including α-amino acids, β-amino acids, indolizidines, pyrrolizidines, eight-membered lactams, and complex natural products is presented. The majority of the reviewed work will be centered in significant results from our research group. However, interesting results from others workers will be included. 1 Introduction 2 Selective Bond Cleavage of the 2-Azetidinone Nucleus 2.1 N1-C2 Bond Breakage 2.2 C2-C3 Bond Breakage 2.3 C3-C4 Bond Breakage 2.4 C4-N1 Bond Breakage 3 Cleavage of Two Bonds of the 2-Azetidinone Ring 4 Summary