Transgenic animal technology has tremendously improved our current comprehension of IGFBP biology. The high potential of IGFBP transgenic mouse models is due to the fact that they mimic elevated serum IGFBP levels, which are diagnosed under the conditions of impaired growth or critical illness. In general, long term elevated levels of IGFBPs in transgenic mouse models almost exclusively resulted in inhibitory phenotypes e.g. of body or organ growth, indicating specific effects in different cell types. This holds especially for the distinct cellular populations present in the bone environment. After establishing transgenic mouse lines modelling permanent increases of IGFBPs, a second question now poses challenge to current functional genome analysis: what is the function of temporary exposure of a certain cell type to isolated IGFBPs? This question is particularly important due to the fact that elevated IGFBP expression is often found in a conditional fashion and in line with the contradictory findings after long or short term IGFBP exposure in rodent models. In order to understand the potential roles of the conditional increases of IGFBP expression, e.g. during illness, and to further study the adaptive or even therapeutic potential of IGFBPs for certain applications like osteoporosis, it is imperative to take a closer look also to the acute effects of the IGFBPs.