Background: The World Health Organization (WHO) s internal guidance for guideline development recommends using Cochrane methods to the extent possible, as well as using the GRADE approach to allow a structured and transparent judgment of the quality of evidence for each outcome of interest. The Cochrane Review Group on HIV/AIDS (CRG) has worked with WHO for nearly 10 years. In 2009, WHO asked the CRG for help in rapidly updating its guidelines for adult and adolescent antiretroviral therapy (ART) and for prevention of mother-to-child HIV transmission (PMTCT). Objectives: To inform the development of two WHO guideline updates by rapidly preparing more than a dozen systematic reviews as well as more than 50 GRADE evidence profiles. Methods: After long-distance discussions with WHO in early 2009 to formulate PICO questions, the CRG assembled 8 review teams and began its work. Expert GRADE consultants provided instruction and ongoing support. The project was finished in time for WHO s consultative meetings in October. Based on the CRG s work and consensus reached at the meetings, WHO released its rapid advice preliminary guidance for both new guidelines in November. Results: Developing PICO questions during in-person meetings may be more efficient than over telephone and e-mail; authors should receive methods training before projects begin; it may be hard to gather enough of the right people to do the work; strategies should be made in advance for obtaining important but not-yet-published data; GRADE evidence profiles for observational data can be complex and tricky to prepare; when devising contractual documents, CRG finance personnel should anticipate bureaucratic delay. WHO requested that in future review projects, a separate abstract be written for each GRADE profile to articulate its data. Conclusions: With sufficient preparation, CRGs can respond effectively to requests for rapid advice from WHO and other policy makers.