This review focuses on the fundamental fluid mechanics which governs the generation of micro/nanospheres. The micro/nanosphere generation process has gathered significant attention in the past two decades, since micro/nanospheres are widely used in drug delivery, food science, cosmetics, and other application areas. Many methods have been developed based on different operating principles, such as microfluidic methods, electrospray methods, chemical methods, and so forth. This paper focuses on microfluidic methods. Although the structure of the microfluidic devices may be different, the operating principles behind them are often very similar. Following an initial discussion of the fluid mechanics related to the generation of microspheres, various design approaches are discussed, including T-junction, flow focusing, membrane emulsification, modified T-junction, and double emulsification methods. The advantages and problems associated with each method are also discussed. Next, the most commonly used computational fluid dynamics (CFD) methods are reviewed at three different levels: microscopic, mesoscopic, and macroscopic. Finally, the issues identified in the current literature are discussed, and some suggestions are offered regarding the future direction of technology development related to micro/nanosphere generation. Few relevant patents to the topic have been reviewed and cited.