IGFBP-2 is an important modulator of IGF availability and activity. It is the second most abundant of the IGFBPs in the circulation and its levels are increased in a variety of tumours and associated with progression and poor prognosis. PTEN is a phosphatase that returns the PI3K/AKT/mTOR pathway to its inactivated state and is therefore a critical modulator of one of the main intracellular signalling pathways activated by the IGFs. Recent evidence has indicated that IGFBP-2 regulates PTEN in a variety of normal and malignant cell types. This review summarises the recent evidence that these extracellular and intracellular modulators are linked to provide a synchronous system for cell regulation with coordinated control of both the 'accelerator' and the 'brake'.