The ability of cells to divide asymmetrically to produce two different cell types provides the cellular diversity found in every multicellular organism. Asymmetric localization of cell-cell junctions and/or intrinsic cell fate determinants and position within specific environment (“niche”) are examples of mechanisms used to specify cell polarity and direct asymmetric divisions. During development, asymmetric divisions provide the basis for establishment of the body axis and cell fate determination in a range of processes. Subsequently, asymmetric cell divisions play a critical role in maintaining adult stem cell populations, while at the same time generating an adequate number of differentiating daughter cells to maintain tissue homeostasis and repair. Loss of cell polarity, and consequently the potential for asymmetric divisions, is often linked to excessive stem cell self-renewal and tumorigenesis. Here we will discuss multiple factors and mechanisms that imbue cells with polarity to facilitate an asymmetric outcome to stem cell divisions, assuring self-renewal and maintenance of the stem cell pool.