Microorganisms in natural and engineered environments interact with surfaces and form aggregates consisting of cells and an extracellular matrix. The design of the process and appropriate operational conditions drive the formation of these biofilms, flocs, and granular structures. The application of granular sludge technologies for nutrient removal is relatively new. Although research and practice benefit from several decades of investigation of biofilm and anaerobic granular sludge systems, a thorough understanding of factors affecting granulation is only beginning to emerge from bench, pilot, and full-scale investigations. Challenges intrinsic to maintaining granular and biofilm structures include management of resistance to substrate transport, establishment of targeted microbial niches, role of extracellular polymeric substances, and impacts of toxic compounds, among others. There is increasing recognition of the potential value of hybrid process configurations that optimize interactions between flocs, granules, and/or biofilm features for process enhancement and robustness. While these structures appear distinct, it is not uncommon to find a mixture of these structures present in a single system and dynamics leading to a transition from one structure to another. The transitions are dependent on changes in the microbial community and properties of the extracellular matrix. This review focuses on the drivers affecting formation and stability of flocs, biofilms, and granules and conditions that support integrated technologies for biological wastewater treatment.