The paper evaluates the power of best-first search over AND/OR search spaces for solving theMost Probable Explanation (MPE) task in Bayesian networks. The main virtue of the AND/OR representation of the search space is its sensitivity to the structure of the problem, which can translate into significant time savings. In recent years depth-first AND/OR Branch-and- Bound algorithms were shown to be very effective when exploring such search spaces, especially when using caching. Since best-first strategies are known to be superior to depth-first when memory is utilized, exploring the best-first control strategy is called for. The main contribution of this paper is in showing that a recent extension of AND/OR search algorithms from depth-first Branch-and-Bound to best-first is indeed very effective for computing the MPE in Bayesian networks. We demonstrate empirically the superiority of the best-first search approach on various probabilistic networks.