The introduction of fluorine atoms into molecules and materials across many fields of academic and industrial research is now commonplace, owing to their unique properties and effects. A particularly interesting feature of fluorine substitution is its impact on the relative orientation of a C?F bond when incorporated with organic molecules. In this Review, we will be shining light on this unique feature by discussing the conformational behaviour of aliphatic carbo- and heterocyclic systems. The conformational preference of each system is associated with various interactions introduced by fluorine substitution such as charge-dipole interactions, dipole-dipole interactions and hyperconjugative interactions. The contribution of each interaction on the stabilization of the fluorinated alicyclic system, which manifests itself in low conformations, will be discussed in details. The novelty of this feature will be demonstrated by presenting the most recent applications.