Background: In response to criticism from methodologists and other stakeholders, the World Health Organization (WHO) recently adopted more rigorous methods for developing its healthcare guidelines and recommendations. WHO sometimes needs to make or update such directives quite quickly, while maintaining rigor in the process. In early 2009, WHO asked the Cochrane HIV/AIDS Group (CRG) for rapid, evidence-based advice on a range of questions concerned with adult antiretroviral therapy. Objectives: Using the GRADE approach, to rapidly prepare for WHO a comprehensive evidence assessment for initial and second-line adult antiretroviral regimens and their respective timing, as well as for when these are complicated by tuberculosis, pregnancy and other issues. Methods: WHO requested guidance on several interrelated research questions about antiretroviral therapy (ART) for adults and adolescents: what to use initially; when to begin it; when to switch it; and what to switch to. The CRG’s Managing Editor asked several Cochrane HIV/AIDS authors worldwide, experts in these respective areas, to participate in the project. After finalizing the research questions and agreeing on the relative importance of specific patient-important outcomes, the authors began their work. Results: Over the period of five months, and for each of the research questions, the CRG will update existing Cochrane reviews, conduct new reviews, prepare GRADE evidence profiles, and develop comprehensive guidance for WHO on these interventions, to the extent that the evidence will permit. WHO will then convene a meeting to agree on a final draft of the new guidelines. Conclusions: WHO may need advice in a time-frame far shorter than the two years or more that is often required for preparing new guidelines. CRGs are well-suited to the task of responding to WHO and other policy maker requests for rigorous, evidence-based guidance on healthcare issues; some CRGs may be able to respond nimbly to requests for rapid advice.