Abstract: Signs and reality are the two fundamental topics of ontology. Reality is whatever exists independently of how we think about it. Signs are those aspects of reality that living things use to interpret, act upon, and communicate about reality. Every signal in a neuron, every thought in a brain, every bit in a computer, and every symbol in any language, natural or artificial, is a sign. Since signs are also part of reality, signs of signs are the part of reality that includes every branch of science including ontology itself. For applied ontology, that distinction is embodied in digital computers: everything in a computer is a sign, either of the outside world or of other signs inside. Aristotle introduced a theory of signs, which he related to language and logic, the medieval Scholastics extended it, and Peirce developed it as the foundation for ontology. His semiotic addresses important issues that have been neglected by the mainstream of 20th century analytic philosophy.