Standardized terminological systems for biomedical information have provided considerable benefits to biomedical applications and research. However, practical use of this information often requires mapping across terminological systems-a complex and time-consuming process. This paper demonstrates the complexity and challenges of mapping across terminological systems in the context of medication information. It provides a review of medication terminological systems and their linkages, then describes a case study in which we mapped proprietary medication codes from an electronic health record to SNOMED CT and the UMLS Metathesaurus. The goal was to create a polyhierarchical classification system for querying an i2b2 clinical data warehouse. We found that three methods were required to accurately map the majority of actively prescribed medications. Only 62.5% of source medication codes could be mapped automatically. The remaining codes were mapped using a combination of semi-automated string comparison with expert selection, and a completely manual approach. Compound drugs were especially difficult to map: only 7.5% could be mapped using the automatic method. General challenges to mapping across terminological systems include (1) the availability of up-to-date information to assess the suitability of a given terminological system for a particular use case, and to assess the quality and completeness of cross-terminology links; (2) the difficulty of correctly using complex, rapidly evolving, modern terminologies; (3) the time and effort required to complete and evaluate the mapping; (4) the need to address differences in granularity between the source and target terminologies; and (5) the need to continuously update the mapping as terminological systems evolve.