The mitotic spindle is mostly perceived as a symmetric structure. However, in many cell divisions, the two poles of the spindle organize asters with different dynamics, associate with different biomolecules or subcellular domains, and perform different functions. In this chapter, we describe some of the most prominent examples of spindle asymmetry. These are encountered during cell-cycle progression in budding and fission yeast and during asymmetric cell divisions of stem cells and embryos. We analyze the molecular mechanisms that lead to generation of spindle asymmetry and discuss the importance of spindle-pole differentiation for the correct outcome of cell division.