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The cell has many ways to regulate the production of proteins. One mechanism is through the changes to the machinery of translation initiation. These alterations favor the translation of one subset of mRNAs over another. It was first shown that internal ribosome entry sites (IRESes) within viral RNA genomes allowed the production of viral proteins more efficiently than most of the host proteins. The RNA secondary structure of viral IRESes has sometimes been conserved between viral species even though the primary sequences differ. These structures are important for IRES function, but no similar structure conservation has yet to be shown in cellular IRES. With the advances in mathematical modeling and computational approaches to complex biological problems, is there a way to predict an IRES in a data set of unknown sequences? This review examines what is known about cellular IRES structures, as well as the …