One widespread mechanism for the generation of diverse cell types is the unequal inheritance of cell fate determinants. Several such determinants have been identified in the fruitfly Drosophila melanogaster and the worm Caenorhabditis elegans and the molecular machinery responsible for their asymmetric segregation is beginning to be unraveled. To divide asymmetrically, cells establish an axis of polarity, orient the mitotic spindle along this axis and localize cell fate determinants to one side of the cell. During cytokinesis, determinants are then segregated into one of the two daughter cells where they direct cell fate. Here, we outline the steps and factors that are involved in this process in Drosophila and C. elegans and discuss their potential conservation in vertebrates.