OBJECTIVES:  Over recent decades the requirement for transparency in data production has led to an explosion in the number of peer review publications. The aim of this research was to evaluate the extent of the literature expansion in three subject areas to highlight challenges posed for performing systematic literature reviews (SLRs). METHODS:  Colorectal cancer, Clostridium difficile infections, and Crohn’s disease were chosen as representative examples of oncology, infectious diseases, and auto-inflammatory diseases, respectively. Searches were performed in Medline (via OVID) to identify the size of the literature, broken down by study design and time period (1996–2000, 2001–2005, 2006–2010, 2011–2015). The strategy combined single MeSH index terms for each disease with study design search filters for SLRs, randomised controlled trials, observational studies, and diagnostic studies developed for use in Medline by SIGN (http://www.sign.ac.uk/methodology/filters.html#diag). RESULTS:  The overall number of published studies and study design type number increased with each 5-year period. For example, in colorectal cancer, clinical trial publications increased two-fold from