A bioreactor is the core of biological processes. To design an appropriate bioreactor system for a particular bioprocess, intensive studies on the biological system, such as cell growth, metabolism, genetic manipulation, and protein or other product expression are needed to understand the cells’ requirement on their physical and chemical environments. It is also necessary to control and optimize the bioreactor environment via operating variables in order to favor the desired functions of cells and achieve cost-effective large-scale manufacture. This article briefly describes fundamental design principles and new types of bioreactors such as centrifugal impeller and wave bioreactors. Bioreactor operation factors and modes including mixing, oxygen supply, shear force, fed-batch, and perfusion cultures are discussed. The trends in bioreactor engineering are also briefly shown.