Aging frailty is a syndrome characterized by a progressive decline in health and clinical symptoms of exhaustion, weight loss, a feeling of slowing down, and a decrease in functional capacity. The biological substrate for frailty is sarcopenia, which is potentiated by chronic inflammation and depletion or impairment of endogenous precursor and stem cells. Current interventions focus on interdisciplinary approaches which include nutritional supplementation, physical exercise, and cognitive intervention. Clinical studies of these preventative approaches have shown inconsistent and modest benefits, further highlighting the unmet clinical need. A variety of pharmacologic and biologic therapies are currently being tested to treat aging. Cell-based therapy represents an attractive option that addresses the pathophysiology of the syndrome. Human allogeneic mesenchymal stem cells (MSCs) which possess immunomodulatory and tissue reparative properties, have been tested in Phase I and Phase II trials. These small early stage studies reveal that allogeneic MSCs administered to frail older adults are feasible to administer, safe and potentially efficacious, ameliorating signs and symptoms of frailty. These studies have formed the basis for larger ongoing trials. Here we review the pathobiology of frailty, and the potential for developing biological strategies to treat this important syndrome.