Converging evidence indicates that peripheral blood (PB) contains stem cells (SCs) with multidifferentiation potential, thus representing a potential source for regenerative medicine in several human disorders, as has also been confirmed by promising results obtained in several preliminary clinical trials. In addition to the classic haematopoietic SCs, PB also harbours endothelial progenitor cells, mesenchymal SCs, tissue-committed SCs and monocyte-like SCs. In spite of a series of different names and/or definitions, a large overlap seems to exist among surface markers, functions and origin of these different SC types. This review analyses the different subsets of SCs described in PB, the different hypotheses suggested to explain their origin, and the possible mechanisms that provide the basis for their biological potential.