The chemical synthesis of secosterols is an arena for the application of C–H functionalization methods as well as C–C manipulations. Studies on the innate reactivity of synthetic intermediates to undergo C–C scissions and rearrangements can shed light on biosynthetic pathways, or, provide proof for biosynthetic proposals. Examples of the authors work (synthesis of the 14,15-secosterol strophasterol A), as well as examples from current literature (Tian’s synthetic work on 13,14:14,15-disecosterols glaucogenins C and D, and Baran’s synthesis of 9,10-secosterol cortistatin A) are discussed.