There is increasing interest in the possibility of eradication of HIV, given the recent case reports. However, it is not clear to what extent brain involvement by HIV poses a challenge to systemic eradication strategies. Areas covered: This review will outline the mechanisms of HIV latency, the various eradication strategies presently under consideration followed by a discussion of the issue of the frequency and severity of brain involvement by HIV. In those patients with HIV brain disease the challenges will be delineated as well as potential approaches to circumvent or minimise them. Expert opinion: Eradication of HIV from the brain using specific methodologies is likely only needed in some patients. However, both the identification of such patients and the details of the necessary methodologies require much more research. ? 2013 Informa UK, Ltd.