This case describes the research methods and procedures that were used for the development of guideline recommendations to reduce HIV-related stigma and discrimination. The major challenge in the project was that there were no previous evidence-based guidelines, nor systematic reviews reported based on the framework suggested by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). This makes the formulation of recommendations challenging. In addition, taking global evidence into a local context requires analysis of contextual and local factors, such as feasibility and acceptability. The project described in this case addressed these challenges through the following research procedures and steps. The first step in the process was invitation of experts through e-mails, telephone, and in-person contacts to establish the guideline panel. Then, we consulted the established panel through informal and formal meetings to determine the scope of the guideline. After that, we conducted a content analysis of documents retrieved from a series of systematic reviews. Following the content analysis, we developed tentative guideline recommendations. We drafted these based on the best available global evidence. For each guideline recommendation, we assigned strength and quality of evidence using a software package developed by the GRADE working group. These guideline recommendations were then evaluated both externally and internally using a series of Delphi surveys. Finally, we explored barriers and facilitators, and other contextual factors that affected the implementation of the guideline, using key informant interviews, and we adapted the guideline by using detailed information obtained from key informants.