The organoselenium-mediated reduction of α,β-epoxy ketones to β-hydroxy ketones has been reported as a new and promissing entry to a variety of acyclic and cyclic aldols. A variety of acyclic and cyclic epoxy ketones smoothly reacted with 3 equiv of PhSeNa in ethanol in the presence of 0.5 equiv of AcOH to give the corresponding β-hydroxy ketones (aldols) in excellent yields. Reaction conditions are neutral and formation of enones (dehydration products) were, if any, less than several percent. In particular, non-formation of enones was observed in the case of acyclic epoxy ketones. This method has been demonstrated to be effective in complex molecules having polyfunctional groups by the successful synthesis of some santanolides such as (+)-dehydro-isoerivanin (3), (+)-isoerivanin (4), (+)-ludovicin C (5), and (+)-1α, 3α-dihydroxyarbusclin B (6). The highly stereoselective total synthesis of (-)-picrotoxinin (10), the most toxic compound of plant origin, was also achieved by the use of this methodology as a key step. The contiguous eight asymmetric centers incorporated in picrotoxinin have been constructed under virtually complete stereoselectivity.