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Background and Overview. High rates of partner change in sex work-whether in professional, 'transactional' or other context-disproportionately drive transmission of HIV and other sexually transmitted infections. Several countries in Asia have demonstrated that reducing transmission in sex work can reverse established epidemics among sex workers, their clients and the general population. Experience and emerging research from Africa reaffirms unprotected sex work to be a key driver of sexual transmission in different contexts and regardless of stage or classification of HIV epidemic. This validation of the epidemiology behind sexual transmission carries an urgent imperative to realign prevention resources and scale up effective targeted interventions in sex work settings, and, given declining HIV resources, to do so efficiently. Eighteen articles in this issue highlight the importance and feasibility of such interventions under four themes: 1) epidemiology, data needs and modelling of sex work in generalised epidemics; 2) implementation science addressing practical aspects of intervention scaleup; 3) community mobilisation and 4) the treatment cascade for sex workers living with HIV. Conclusion. Decades of empirical evidence, extended by analyses in this collection, argue that protecting sex work is, without exception, feasible and necessary for controlling HIV/STI epidemics. In addition, the disproportionate burden of HIV borne by sex workers calls for facilitated access to ART, care and support. The imperative for Africa is rapid scale-up of targeted prevention and treatment, facilitated by policies and action to improve conditions where sex work takes place. The opportunity is a wealth of accumulated experience working with sex workers in diverse settings, which can be tapped to make up for lost time. Elsewhere, even in countries with strong interventions and services for sex workers, an emerging challenge is to find ways to sustain them in the face of declining global resources. © 2015 Steen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.