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The hard link concept is simpler and much more straightforward than the neighboring approaches described above. Hard links are applied between entries in different databases and exist wherever there is a logical connection between entries. For instance, if a PubMed entry describes the sequencing of a chromosomal region containing a gene of interest, a hard link is established between the PubMed entry and the corresponding nucleotide entry for that gene. If an open reading frame in that gene codes for a known protein, a hard link is established between the nucleotide entry and the protein entry. If the protein entry has an experimentally deduced structure, a hard link would be placed between the protein entry and the structural entry.

Searches can begin anywhere within the Entrez ecosystem – there are no constraints on the user as to where the foray into this information space must begin. However, depending on which database is used as the jumping-off point, different database fields will be available for searching. This stands to reason, as the entries in different databases are necessarily organized differently, reflecting the biological nature of the entities that each database is trying to catalog.