In this paper, we present a systematic methodology for designing Reconfigurable Machine Tools (RMTs). The synthesis methodology takes as input a set of functional requirements — a set of process plans and outputs a set of kinematically-viable reconfigurable machine tools that meet the given design specifications. We present a mathematical framework for synthesis of machine tools using a library of building blocks. The framework is rooted in (a) graph theoretic methods of enumeration of alternate structural configurations and (b) screw theory that enables us to manipulate matrix representations of motions to identify appropriate kinematic building blocks. The methodology described in this paper provides a mathematical framework to address dynamic stiffness, and accuracy prediction of the kinematically-viable designs that are generated by the synthesis procedure. This methodology has been implemented in a program, called PREMADE (PRogram for REconfigurable MAchine tool DEsign), and the results are validated against commercial machine tool designs.