This Focus Review presents recent developments in the cleavage of C-C bonds in organic molecules. Significant progress in C-C activation, including the development of a variety of new synthetic strategies, has contributed to the development of this field over the past few decades. Transition-metal-mediated C-C bond cleavage has been shown to be a quite efficient process and several elegant metal-free methods have also recently been developed. Strained rings have been widely used in C-C cleavage transformations; however, unstrained C-C activation has increasingly caught the attention of organic researchers, which inspired us to clarify the developments in this field.