Through casual observations, formal consultations, and educational sessions, the authors have identified various indexing features of the National Library of Medicine's Medical Subject Headings (MeSH) that pose challenges to end users while attempting to obtain relevant retrieval when searching MEDLINE. These problematic features include the use of Explodes, Tree structures, subheadings, Text Word vs. subject heading searching, and central concept searching. End-user search software is becoming more sophisticated with an increasing number of choices offered for search strategy formulation. Methods of instruction to orient the end user to these systems will also have to become more detailed. A review of the literature, that discusses end-user problems with using MEDLINE and MeSH, is included.