Microchimerism (Mc) refers to the harboring of a small number of cells (or DNA) that originated in a different individual. Naturally acquired Mc derives primarily from maternal cells in her progeny, or cells of fetal origin in women. Both maternal and fetal Mc are detected in hematopoietic cells including T and B cells, monocyte/macrophages, natural killer (NK) cells and granulocytes. Mc appears also to generate cells such as myocytes, hepatocytes, islet β cells and neurons. Here, the detrimental and beneficial potential of Mc is examined. The prevalence, diversity and durability of naturally acquired Mc, including in healthy individuals, indicates that a shift is needed from the conventional paradigm of ‘self versus other’ to a view of the normal ‘self’ as constitutively chimeric.