Human mesenchymal stromal cells (hMSCs) offer great potential for bone tissue engineering applications, but their in vivo performance remains limited. Pre-conditioning of these cells with small molecules to improve their differentiation prior to implantation or incorporation of growth factors are possible solutions. Insulin-like growth factor-1 (IGF-1) is one of the most abundant growth factors in bone, involved in growth, development and metabolism, but its effects on hMSCs are still subject of debate. Herein, we examined the effects of IGF-1 on proliferation and differentiation of hMSCs in vitro and we found that serum abolished the effects of IGF-1. Only in the absence of serum, IGF-1 increased proliferation, ALP expression and osteogenic gene expression of hMSCs. Furthermore, we examined synergistic effects of BMP-2 and IGF-1 and, although IGF-1 enhanced BMP-2-induced mineralization, IGF-1 only slightly affected in vivo bone formation.