We introduce a new paradigm in the computer architecture referred to as Polymorphic Instruction Set Computers (PISC). This new paradigm, in difference to RISC/CISC, introduces hardware extended functionality on demand without the need of ISA extensions. We motivate the necessity of PISCs through an example, which arises several research problems unsolvable by traditional architectures and fixed hardware designs. More specifically, we address a new framework for tools, supporting reconfigurability; new architectural and microarchitectural concepts; new programming paradigm allowing hardware and software to coexist in a program; and new spacial compilation techniques. The paper illustrates the theoretical performance boundaries and efficiency of the proposed paradigm utilizing established evaluation metrics such as potential zero execution (PZE) and the Amdahl’s law. Overall, the PISC paradigm allows designers to ride the Amdahl’s curve easily by considering the specific features of the reconfigurable technology and the general purpose processors in the context of application specific execution scenarios.