The response of cells to ionising radiation has been extensively studied for the past 30 years. When radiation is absorbed in biological material, it can directly ionise a critical site (direct effect) or interact with other molecules to produce reactive free radicals, which can subsequently damage critical biological molecules (indirect effect). DNA is considered the critical target damaged by ionising radiation by both direct and indirect processes. Since radiotherapy had proven to be effective in the treatment of non-malignant proliferative processes, it was assumed that this adjunctive treatment would also inhibit vascular restenosis. The major difference between external and intravascular radiation is dose distribution. Intravascular delivery results in extremely high doses to the lumen with a fall-off in dose as a function of distance from the source; whereas, external beam would deliver a uniform dose over the entire volume of tissue treated. Unlike in the coronary circulation most of the peripheral vessels treated are greater than 3 mm in diameter; in fact many are 7 to 10 mm in diameter. Since beta radiation is related to lower penetration properties and more heterogeneous distribution of radiation in comparison to gamma radiation, it is therefore necessary to use a gamma radiation source because it would be difficult to irradiate the sub-intimal tissue with a beta source centred in a large vessel. Radiation can and does have the potential to destroy blood vessels. The challenge in vascular brachytherapy is to treat blood vessels to a point where restenosis is inhibited; yet the vessel is not irreparably damaged.