Traditionally, most physicians would seek answers to their questions using paper resources such as textbooks, systematic reviews, or journal articles. These sources of medical knowledge are commonly referred to as Knowledge Based Information (KBI). As the Electronic Health Record (EHR) becomes more commonplace there is a great opportunity to link these KBI sites with the EHR and bring relevant KBI to the point of care. However, in order for this connection to occur, there needs to be agreement as to the syntax and semantics of the communication between these two types of systems. This can be accomplished through the standardization and adoption of interoperability protocols. This paper will discuss the general issues surrounding the interoperability of KBI and healthcare and provide a technical comparison of the three protocols: Z39.50 Information Retrieval standard, the Open Archives Initiative, and the Simple Digital Library Interoperability Protocol.