These algorithms primarily focus on generating geometrically diverse, low-energy conformers, which are important to many applications including structure-based virtual screening, pharmacophore modeling, and generating 3D quantitative structureactivity relationships (QSAR). In this paper, we mainly focus on finding the lowestenergy conformation of a molecule instead of achieving geometric diversity. The energy landscape is effectively unknown a priori, without exhaustive -and sometimes expensive -energy evaluation. Therefore, intelligent search strategies are needed to find the lowest energy state, and its associated conformation, in the shortest time possible. Most methods perform well if the number of rotatable bonds is small, typically four or fewer. The combinatorial explosion that arises with more flexible molecules, however, makes finding this global optimum increasingly more challenging.