In the last two decades, Field Programmable Gate Arrays (FPGAs) have been rapidly developed from simple “glue-logic” to a powerful platform capable of implementing a System on Chip (SoC). Modern FPGAs achieve not only the high performance compared with General Purpose Processors (GPPs), thanks to hardware parallelism and dedication, but also better programming flexibility, in comparison to Application Specific Integrated Circuits (ASICs). Moreover, the hardware programming flexibility of FPGAs is further harnessed for both performance and manipulability, which makes Dynamic Partial Reconfiguration (DPR) possible. DPR allows a part or parts of a circuit to be reconfigured at run-time, without interrupting the rest of the chip’s operation. As a result, hardware resources can be more efficiently exploited since the chip resources can be reused by swapping in or out hardware tasks to or from the chip in a time-multiplexed fashion. In addition, DPR improves fault tolerance against transient errors and permanent damage, such as Single Event Upsets (SEUs) can be mitigated by reconfiguring the FPGA to avoid error accumulation. Furthermore, power and heat can be reduced by removing finished or idle tasks from the chip. For all these reasons above, DPR has significantly promoted Reconfigurable Computing (RC) and has become a very hot topic. However, since hardware integration is increasing at an exponential rate, and applications are becoming more complex with the growth of user demands, highlevel application design and low-level hardware implementation are increasingly separated and layered. As a consequence, users can obtain little advantage from DPR without the support of system-level middleware. To bridge the gap between the high-level application and the low-level hardware implementation, this thesis presents the important contributions towards a Reliable, Reconfigurable and Real-Time Operating System (R3TOS), which facilitates the user exploitation of DPR from the application level, by managing the complex hardware in the background. In R3TOS, hardware tasks behave just like software tasks, which can be created, scheduled, and mapped to different computing resources on the fly. The novel contributions of this work are: 1) a novel implementation of an efficient task scheduler and allocator; 2) implementation of a novel real-time scheduling algorithm (FAEDF) and two efficacious allocating algorithms (EAC and EVC), which schedule tasks in real-time and circumvent emerging faults while maintaining more compact empty areas. 3) Design and implementation of a faulttolerant microprocessor by harnessing the existing FPGA resources, such as Error Correction Code (ECC) and configuration primitives. 4) A novel symmetric multiprocessing (SMP)-based architectures that supports shared memory programing interface. 5) Two demonstrations of the integrated system, including a) the K-Nearest Neighbour classifier, which is a non-parametric classification algorithm widely used in various fields of data mining; and b) pairwise sequence alignment, namely the Smith Waterman algorithm, used for identifying similarities between two biological sequences. R3TOS gives considerably higher flexibility to support scalable multi-user, multitasking applications, whereby resources can be dynamically managed in respect of user requirements and hardware availability. Benefiting from this, not only the hardware resources can be more efficiently used, but also the system performance can be significantly increased. Results show that the scheduling and allocating efficiencies have been improved up to 2x, and the overall system performance is further improved by ~2.5x. Future work includes the development of Network on Chip (NoC), which is expected to further increase the communication throughput; as well as the standardization and automation of our system design, which will be carried out in line with the enablement of other high-level synthesis tools, to allow application developers to benefit from the system in a more efficient manner.