This chapter explores both the usefulness and the limits of the machine metaphor applied to living organisms. To do so, it develops a framework advanced by Howard Pattee, a crucial component of which is the notion of constraint. According to classical mechanics, macroscale objects, including mechanisms, result from constraints that limit the degrees of freedom of their components and enable these objects to exhibit specific capacities. When free energy is available, constraints determine what work a mechanism will perform. Some constraints in mechanisms are flexible and enable other mechanisms to operate on them. When the activities of these second mechanisms are initiated by information, they can perform a control function. A critical difference between machines and biological mechanisms is where control is lodged – in an external agent or within the organism. Control mechanisms in organisms serve to regulate biological mechanisms so that they operate to build and repair the organism or continue its lineage. A second difference follows: whereas control of machines is commonly organized hierarchically, topping out with the human user, control mechanisms in organisms often form heterarchical networks, with multiple control mechanisms operating on the same production or control mechanism. Examples involving signaling systems in single-celled organisms and nervous systems in multicellular organisms are developed.