The reliability of RFID systems depends on a number of factors including: RF interference, deployment environment, configuration of the readers, and placement of readers and tags. While RFID technology is improving rapidly, a reliable deployment of this technology is still a significant challenge impeding wide-spread adoption. This research investigates system software solutions for achieving a highly reliable deployment that mitigates inherent unreliability in RFID technology. We have considered two different problem domains for large scale RFID deployment. One is item tracking and the other is guidance-monitoring. Item tracking considers applications that have statically placed RFID readers to observe the RFID tagged objects in motion. An airport scenario to observe the tagged baggage or warehouse scenarios to track the tagged goods are examples of item tracking applications. A self guided tour, search and rescue scenario or a visually impaired person looking for direction and guidance in a tagged environment are examples of item location applications. It is observed that there is a notion of path that follows the direction and flow of the mobile items in the item tracking applications and a path gets created along the direction and flow of the mobile object in item location applications. A system level knowledge of the data flow can benefit the system in different aspects such as improved reliability, resource management and real time response. We have designed and implemented an RFID middleware for item tracking: RF²ID (Reliable Framework for Radio Frequency Identification) to organize and support queries over data streams in an efficient manner. We have developed (1) a virtual reader abstraction to improve the potentially error-prone nature of reader generated data (2) a novel path abstraction to capture the logical flow of information among virtual readers. Prototype implementation using both RFID readers and simulated readers using an empirical model of RFID readers show that RF²ID is able to provide high reliability, support path-based object detection and use efficient resource management techniques. We propose a middleware solution that takes into account the data flow information for item location application that requires real time response. The guidance-monitoring scenario considers mobile RFID readers that traverse in a tagged environment. We consider the scenario of an Assisted Living Center for elderly residents as a motivating guidance-monitoring application. The solution for guidance-monitoring system is called GuardianAngel. The application scenario considers a tagged indoor environment with residents having their own RFID readers to provide them with adequate information about the surroundings. The guidance and monitoring requirement can be conflicting. The guidance information requires very fine grain information about the environment to make proper decisions. On the other hand, the monitoring system must not have a fine grain knowledge which can introduce concerns such as privacy concerns. We consider this aspect during the design and implementation. The system is a two layered infrastructure that has the upper layer which is the monitoring layer. This layer is in charge of monitoring of the actors in the environment. The monitoring layer is physically a set of distributed virtual stations that have the knowledge about the environment. The environment itself is equipped with RFID tags. The residents of the environment have the mobile object that has a sensing element and a computing element (e.g., handhold device with a portable RFID reader) - the guidance server runs on this mobile object. The guidance server is in charge of making local decisions to the users. It is resource limited and asks for new information from the virtual stations as needed. The guidance server also provides the monitoring server with the information regarding the status of the mobile object. But the status information is not fine grain information - the guidance server wraps up the information over a period of time and over a larger region to hide the detailed information of the users.The system uses the logical path based abstraction to guide the users. We have implemented the real testbed using grid structured RFID devices along with scalability study using emulated RFID readers. The basic contribution of our work is based on providing novel middleware solution that is able to serve the application taking into account the inherent unreliability of RFID technology. Our path abstraction that uses the physical flow of data as an ally to generate a logical system level flow enhances the performance in many ways.