INTRODUCTION Could injectable cabotegravir (CAB‐LA) be the game changer for HIV prevention that the world has been waiting for—especially low‐ and middle‐income countries (LMICs) with high HIV prevalence? And what [...], : Introduction: The proven effectiveness of injectable cabotegravir (CAB‐LA) is higher than that of any other HIV prevention intervention ever trialled or implemented, surpassing medical male circumcision, condoms and combination antiretroviral treatment. Based on our own analyses and experience with the South African oral pre‐exposure prophylaxis (PrEP) programme, we review the supply and demand side factors that would need to be in place for a successful rollout of CAB‐LA, and delineate lessons for the launch of other long‐acting and extended delivery (LAED) antiretroviral drugs. Discussion: On the supply side, CAB‐LA will have to be offered at a price that makes the drug affordable and cost‐effective to low‐ and middle‐income countries, especially those with high HIV prevalence. An important factor in lowering prices is a guaranteed market volume, which in turn necessitates the involvement of large funders, such as PEPFAR and the Global Fund, and a fairly rapid scale‐up of the drug. Such a scale‐up would have to involve speedy regulatory approval and WHO pre‐qualification, swift integration of CAB‐LA into national guidelines and planning for large enough manufacturing capacity, including the enabling of local manufacture. On the demand side, existing demand for HIV prevention products has to be harnessed and additional demand created, which will be aided by designing CAB‐LA programmes at the primary healthcare or community level, and involving non‐traditional outlets, such as private pharmacies and doctors’ practices. Conclusions: CAB‐LA could be the game changer for HIV prevention that we have been hoping for, and serve as a useful pilot for other LAEDs. A successful rollout would involve building markets of a guaranteed size; lowering the drug's price to a level possibly below the cost of production, while also lowering the cost of production altogether; harnessing, creating and sustaining demand for the product over the long term, wherever possible, in national programmes rather than single demonstration sites; and establishing and maintaining manufacturing capacity and supply chains. For this, all parties have to work together—including originator and generic manufacturers, donor organizations and other large funders, and the governments of low‐ and middle‐income countries, in particular those with high HIV prevalence.