<p>For countless organisms, we know their genomes as long sequences of A’s, C’s, G’s, and T’s. But what does this information – if it is information – <i>mean</i>? This is a question of semantics, while information theory, as introduced by Shannon (1948), explicitly is not concerned with meaning. This has led many scholars within theoretical biology and biosemiotics to disregard information theory as irrelevant. By discussing the case of molecular motifs from the points of view of bioinformatics and biosemiotics, we offer an interpretation of biological information that emphasizes the usefulness of Shannon’s theory of information to understand aspects of the generation and interpretation of meaning in living cells. Though the semantic aspects of information were not dealt with by Shannon, contributions to bioinformatics including the work of Thomas D. Schneider and colleagues have shown how the information content of a site, defined as the decrease in uncertainty upon binding, is often just enough to locate the sites in the genome. This&#xa0;provides a better understanding of the biosemiotics of sequence information and the interdependency of information transfer, memory, biochemical specificity, biofunction, and meaning. Thus, we argue that the quantitative approach to information by Schneider is compatible with biosemiotics and Bateson’s definition of information as “a difference that makes a difference”.</p>