The paper presents and evaluates the power of best-first search over AND/OR search spaces in graphical models. The main virtue of the AND/OR representation is its sensitivity to the structure of the graphical model, which can translate into significant time savings. Indeed, 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. In this paper we introduce two classes of best-first AND/OR search algorithms: those that explore a context-minimal AND/OR search graph and use static variable orderings, and those that use dynamic variable orderings but explore an AND/OR search tree. The superiority of the best-first search approach is demonstrated empirically on various real-world benchmarks.