The versatility of modern manufacturing is ever-increasing. Reconfigurable manufacturing systems are one proposed solution to offer concurrent flexibility and productivity and enable manufacturing systems to adapt to rapidly changing requirements. However, modern machine tools do not fully comply with the requirements of the reconfigurability paradigm. One reason lies in the limited changeability of the machine tool frame itself, as machine tool frames are usually designed as platforms with a limited set of predefined configurations. This thesis presents a mechatronic building block system for the modularization of machine tool frames. The building block system consists of passive, smart, and active building blocks. Following a bottom-up approach, the research starts with the idea of tessellating the machine tool frame with a suitable polyhedral geometry. A novel methodology is used to grade several geometries and leads to the selection of the hexagonal prism as the basic building block geometry. The investigations proceed with the design and experimental investigation of the individual building blocks and concludes with the configuration and realization of a modular and reconfigurable three-axis milling machine tool.