 The desire to understand how the organization in cells and multicellular organisms differs from that found in most naturally occurring systems or human-made artifacts motivated a body of research in theoretical biology in the 1970s and 1980s. Among the most prominent contributors to theoretical biology were Pattee (many of his most important papers have been collected in Pattee 2012), Rosen (1985, 1991), Polanyi (1968), and Waddington (1961). Philosophy of biology, as it developed as a specialty in philosophy of science in the 1970s and 1980s, largely ignored this tradition. Today however a number of philosophers concerned with cell biology are drawing upon its insights. Here we focus on one key conceptual tool theoretical biologists provide for understanding the distinctive activities of living systems such as cells: constraints. The notion of constraint is drawn from classical mechanics, where constraints serve to constitute macro-scale objects from their micro-scale particles. Constraints thus account for why macro-scale objects exhibit different properties than their constituents. Constraints are not explained by laws but rather serve as boundary conditions that must be ascertained empirically. Accordingly, to the degree constraints explain biological activities of cells, these activities cannot be reduced, in the sense of being derived from the principles of chemistry or physics. Instead, researchers must, on the basis of empirical inquiry, identify the constraints actually realized in living cells.