Multipotent mesenchymal stromal cells [also referred to as mesenchymal stem cells (MSCs)] are a heterogeneous subset of stromal cells. They can be isolated from bone marrow and many other types of tissue. MSCs are currently being tested for therapeutic purposes (i.e., improving hematopoietic stem cell engraftment, managing inflammatory diseases and regenerating damaged organs). Their tropism for tumors and inflamed sites and their context-dependent potential for producing trophic and immunomodulatory factors raises the question as to whether MSCs promote cancer and/or infection. This article reviews the effect of MSCs on tumor establishment, growth and metastasis and also susceptibility to infection and its progression. Data published to date shows a paradoxical effect regarding MSCs, which seems to depend on isolation and expansion, cells source and dose and the route and timing of administration. Cancer and infection may thus be adverse or therapeutic effects arising form MSC administration.