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Mesenchymal stem cells (MSCs) were initially identified as progenitors of skeletal tissues within mammalian bone marrow and cells with similar properties were also obtained from other tissues such as adipose and dental pulp. Although MSCs have been extensively investigated, their native behavior and in vivo identity remain poorly defined. Uncovering the in vivo identity of MSCs has been challenging due to the lack of exclusive cell markers, cellular alterations caused by culture methods, and extensive focus on in vitro properties for characterization. Although MSC site of origin influences their functional properties, these mesenchymal progenitors can be found in the perivascular space in virtually all organs from where they were obtained. However, the precise identity of MSCs within the vascular wall is highly controversial. The recurrent concept that MSCs correspond to pericytes in vivo has been supported mainly by their perivascular localization and expression of some molecular markers. However, this view has been a subject of controversy, in part, due to the application of loose criteria to define pericytes and due to the lack of a marker able to unequivocally identify these cells. Furthermore, recent evidences indicate that subpopulations of MSCs can be found at extravascular sites such as the endosteum. In this opinion review, we bring together the advances and pitfalls on the search for the in vivo identity of MSCs and highlight the recent evidences that suggest that perivascular MSCs are adventitial cells, acting as precursors of pericytes and other stromal cells during tissue homeostasis.