Recent developments in the stereoselective synthesis of polysubstituted cyclopropanes nowadays allow chemists to easily access these strained rings with high diastereo- and enantiomeric ratios. In turn, this development has created a paradigm shift for the synthesis of stereodefined acyclic molecules though selective carbon-carbon bond cleavage. Through chosen illustrative examples, we aim to show in this review that the cleavage of cyclopropane is a powerful approach to reveal sp(3) stereocenters in acyclic systems. The application of these concepts was illustrated by the total syntheses of several natural products and other important molecules, further showing the power of these strategies as a powerful tool in organic synthesis.