Asymmetric cell division (ACD) is a mechanism to generate cellular diversity and used by prokaryotes and eukaryotes alike. Stem cells in particular rely on ACD to self-renew the stem cell while simultaneously generating a differentiating sibling. It is well established that the differential partitioning of cell fate determinants in the form of RNA and proteins between sibling cells induces changes in cell behavior and fate. Recently, insight into molecular mechanisms has been gained that could explain how centrosomes and centrosome-associated structures such as histones, chromosomes or the primary cilium, segregate asymmetrically. Similarly, many cell types also generate physical asymmetry in the form of sibling cell size differences. Emerging data suggests that spindle-induced cleavage furrow positioning through regulated spindle placement and spindle geometry is insufficient to explain all occurrence of cell-size asymmetry. Instead, asymmetric membrane extension based on asymmetric Myosin localization and cortical remodeling could be a driving force for the generation of physical asymmetry.