Biosemiotics belongs to a class of approaches that provide mental models of lifesince it applies some semiotic concepts in the explanation of natural phenomena. Such approaches are typically open to anthropomorphic errors. Usually, the main source of such errors is the excessive vagueness of the semiotic concepts used. If the goal of biosemiotics is to be accepted as a science and not as a priorimetaphysics, it needs both an appropriate source of the semiotic concepts and a reliable method of adjusting them for biosemiotic use. Charles S. Peirce's philosophy offers a plausible candidate for both these needs. Biosemioticians have adopted not only Peirce's semiotic concepts but also a number of metaphysical ones. It is shown that the application of Peirce's basic semiotic conceptions of sign and sign-process (semiosis) at the substantial level of biosemiotics requires the acceptance of certain metaphysical conceptions, i.e. Tychismand Synechism. Peirce's method of pragmaticism is of great relevance to biosemiotics: 1. Independently of whether Peirce's concepts are used or even applicable at the substantial level of biosemiotics, Peirce's method remains valuable in makingbiosemiotics and especially in adjusting its basic concepts. 2. If Peircean semeiotic or metaphysics is applied at the substantial level of biosemiotics, pragmaticism is valuable in clarifying the meaning and reference of the applied Peircean concepts. As a consequence, some restrictions for the application of Peirce in biosemiotics are considered and the distinction of Peirce's philosophy from the 19th century idealistic Naturphilosophieis emphasized