Culture in any of its definitions is based on one specifically human capacity—the making, using, and abandoning signs. Signs are the arena for semiotics—the science of signs. Human lives are meaningful—and all meanings are based on signs. Signs are the focus of the science of semiotics. Semiotics emerged at the end of the nineteenth century, in parallel in North America and in Europe. In the former tradition, it was built on the philosophical and mathematical integration of ideas of Charles Sanders Peirce (born on September 10, 1839—died on April 19, 1914), who was one of the institutionally barely tolerated leading scholars in the late nineteenth century United States. He was an independent thinker nor accepting institutionalized “truths.” Institutions anywhere in the world set up expectations for personal loyalties for their functionaries that often involve dislike of voices of persons who are not following the social norms. Peirce was one of those conscientious critics of his contemporary American universities, and as a result could find no job in academia. This chapter includes elaboration of basic concepts of semiotics as applied in cultural psychology. Persons make signs—utilizing their sign-construction history—under the guidance of other human beings who are collectively guided in this meaning-making enterprise by different social institutions. The focus in this book is on how the interface between these social units and active semiotic agents—persons living their lives—is structured.