Three major pillars have until recently stood as unquestioned assumptions of modern biology (the Modern Synthesis): 1) externalism, i. e., that internal properties of organisms are explained exclusively in terms of properties of their external environments, natural selection pressures, 2) gradualism, and 3) gene centrism. Recent developments in molecular genetics, cell biology and developmental biology implies that these three pillars cannot remain uncontested. Of the three pillars externalism is probably the more fundamental and the one that poses the strongest challenge to our intuitive experience of agency as an inherent property of life. Biologist of today embraces natural selection theory because it opens the doors for biology to become an exact science. In the same time, however, biology seems unable to get rid of teleological language which implicitly contradicts the non-agency premise of externalism and yet keeps popping everywhere. Biosemiotics is based on an understanding of organismic agency as real, as a property that is ultimately rooted in the capacity of cells and organisms to interpret (consciously or unconsciously) events or states as referring to something other than themselves or, in other words, the capacity to interpret signs. These signs need not be emitted with a purpose of communication, in fact by far the most signs are not part of a sender-receiver interaction but are simply important cues (internal or external) that organisms use to guide their activities. The chapter unfolds this semiotic view of life and explores the ontological implications and consequences of the position.