Knowledge-Based Systems (KBSs) represent a relatively new programming approach and methodology that has evolved and is still evolving as an important sub-area of Artificial Intelligence (AI) research. The most prevalent application of KBSs, which emerged in recent times, has been various types of diagnosis and troubleshooting. KBS has an important role to play, particularly in fault diagnosis of process plants, which involve lot of challenges starting from commonly occurring malfunctions to rarely occurring emergency situations. The KBS approach is promising for this domain as it captures efficient problem-solving of experts, guides the human operator in rapid fault detection, explains the line of reasoning to the human operator, and supports modification and refinement of the process knowledge as experience is gained. However, most of the current KBSs in process plants are built on expert knowledge compiled in the form of production rules. These systems lack flexibility due to their process-specific nature and are unreliable when faced with unanticipated faults. Although attempts have been made to integrate knowledge based on experience and 'deep' process knowledge to overcome this lack of flexibility, very little work has been reported to make the diagnostic system flexible and usable for various plant configurations. In this thesis, we propose a hybrid knowledge framework which includes both process-specific and process-common knowledge of the structure and behavior of the domain, and a process-independent diagnostic mechanism based on causal and qualitative reasoning. This framework is flexible and allows a unified design methodology for fault diagnosis of process plants. The process-specific knowledge includes experiential knowledge about commonly occurring faults, behavioral knowledge about causal interactions among process-dependent variables, and structural knowledge about components' description and connectivity. The process-common knowledge comprises template models of various types of components commonly present in any process plant, constraints and confluences based on mass and energy balances between parameters across components. The process behavioral knowledge is qualitatively represented in the form of Signed Digraph (SDG), which is converted into a set of rules (SDGrules), added with control premises for the purpose of diagnostic reasoning. Frame-objects are used to represent the structural knowledge, while rules are used to capture experiential knowledge about common faults. An interface program viz., Knowledge Acquisition Interface (KAI) aids acquisition and conversion of (i) behavioral knowledge into a set of SDG-rules and (ii) structural knowledge and experience-based heuristic rules into a set of facts. The Diagnostic Mechanism is based on a steady state model of the process and is composed of three consecutive phases for locating a fault. The first phase is Malfunction Block Identification (MBT), which locates a malfunctioning subsystem or Malfunction Block (MB) that is responsible for causing the process malfunction. It is based on alarm data whenever violation of process parameters occurs. Once the suspected MB is identified, the second phase viz., Malfunction Parameter Identification (MPI) is invoked t o locate parameters which indicate the prime cause(s) of the fault in that MB. This is achieved by correlating various instrumentation data through causal relationships described by the SDG-rules of that MB. Finally, Malfunctioning Component Identification (MCI) phase is invoked to locate the malfunctioning component. MCI phase uses the malfunction parameter (s) obtained from previous phase and experiential and structural knowledge of that MA for this purpose. The Diagnostic Mechanism is process-independent and, therefore, is capable of adapting to various types of plant configurations. Since, the Knowledge Base and the Diagnostic Mechanism are separate, modification of either of them can be done independently. The Diagnostic Mechanism is potentially capable of investigating symptoms that have multiple or unrelated origins. It also provides explanation facility for justifying the line of diagnostic reasoning to the human operator.