It is hard to treat fine tailings resulting from oil sands extraction processes. No current fine tailings treatment technology can completely eliminate tailings ponds, despite considerable efforts to address the slow settling of fines and to facilitate the consolidation of sediments. Some treatments use coagulants and coarse solids to form composite or consolidated tailings; others use polymer flocculants. The performance of polymer flocculants is evaluated empirically, with fine tailings often being considered as a black box. Some fundamental studies use single clay systems, such as kaolinite suspended in water, as models to evaluate the performance of polymer flocculants. While it is easier to relate polymer performance to specific conditions in these simpler systems, it is difficult to translate these results to the treatment of the much more complex tailings environment. For the rational design of polymer flocculants, one must understand the interactions between polymers and the several components in tailings. With this information in hand, one can optimize the molecular structure of polymer flocculants to treat oil sands tailings efficiently. In this review, we summarize the published research on flocculation performance within the context of complex fine tailings systems. Furthermore, we describe the compositional complexity of mature fine tailings to help the design of more representative model tailings systems.