Background: Multiple and concurrent sexual partnerships have been identified as southern Africa’s key behavioural driver of HIV, resulting in calls to make partner reduction programming central to an intensified HIV prevention focus. Various efforts are currently being made in the region in response to this call. Such efforts will likely have as limited success as past prevention efforts if the cultural milieu in which sexual partnering practices are located and reproduced remains poorly understood, unaccounted for, and unaddressed in prevention programming. Methods: Focussed ethnographic discussions were held between October 2007 and November 2008 with 228 members of southern African non-government organisations representing seven countries. Discussions formed part of follow-up activities to a high level regional meeting and were aimed at exploring contextual factors in HIV transmission, most especially the role of culture in relation to multiple and concurrent partnerships. Results: Common patterns in cultural scripts for the performance of sexuality were discernable. Several predominant scripts that tend to affirm and lend cultural legitimacy to multiple and concurrent partnering were identified, discussed and analysed. Conclusion: Effectuating change at the level of cultural scripting to discourage multiple and concurrent partnerships is required for sustainable long-term protection of people and communities against HIV. The success of partner reduction programs will be largely determined by the extent to which they are informed by anthropological knowledge and work with cultural logics to allow people to envision how they can transform obstacles into support for risk reduction.