This chapter outlines a broad theory of sign use in natural and artificial systems that was developed over several decades within the context of theoretical biology, cybernetics, systems theory, biosemiotics, and neuroscience. Different conceptions of semiosis and information in nature are considered. General functional properties of and operations on signs, including measurement, computation, and sign-directed actions are described. A taxonomy of semiotic systems is built up from combinations of these operations. The respective functional organizations and informational capabilities of formal systems and computempiral-predictive scientific models, percept-action systems, purposive goal-seeking systems, and self-constructing systems are discussed. Semiotic relations are considered in terms of Morrisean semiotic triad of syntactics, semantics, and pragmatics. Analysis of statetransition structure is used to demarcate functional boundaries, such as epistemic and control cuts. Capabilities for open-ended behavior, combinatoric and emergent creativity, and umwelt expansion are taken up. Finally, basic problems of neurosemiotics, neural coding, and neurophenomenology are outlined.