Abstract Background Over the past few years, information retrieval has become more and more professionalized, and information specialists are considered full members of a research team conducting systematic reviews. Research groups preparing systematic reviews and clinical practice guidelines have been the driving force in the development of search strategies, but open questions remain regarding the transparency of the development process and the available resources. An empirically guided approach to the development of a search strategy provides a way to increase transparency and efficiency. Methods Our aim in this paper is to describe the empirically guided development process for search strategies as applied by the German Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, or "IQWiG"). This strategy consists of the following steps: generation of a test set, as well as the development, validation and standardized documentation of the search strategy. Results We illustrate our approach by means of an example, that is, a search for literature on brachytherapy in patients with prostate cancer. For this purpose, a test set was generated, including a total of 38 references from 3 systematic reviews. The development set for the generation of the strategy included 25 references. After application of textual analytic procedures, a strategy was developed that included all references in the development set. To test the search strategy on an independent set of references, the remaining 13 references in the test set (the validation set) were used. The validation set was also completely identified. Discussion Our conclusion is that an objectively derived approach similar to that used in search filter development is a feasible way to develop and validate reliable search strategies. Besides creating high-quality strategies, the widespread application of this approach will result in a substantial increase in the transparency of the development process of search strategies.