Deep knowledge about process behaviors plays an important role in the diagnosis of chemical processes. Cause-and-effect reasoning using deep knowledge is useful especially for interacting malfunctions. This work explores the integration of deep knowledge into task-specific, knowledge-based architectures for resolving interacting multiple malfunctions and presents a novel methodology called diagnostically focused simulation (DFS). Invoked in an auxiliary manner, DFS uses deep knowledge and performs qualitative simulation in a highly constrained manner. The close integration with other problem solvers is an evolutionary approach to using qualitative simulation in diagnosis and manages a normally computationally-explosive procedure. Diagnostic results from the compiled problem solver provide a situation-specific assessment of the chemical process, identify possible malfunction scenarios, and focus on appropriate levels of process detail. DFS effectively demonstrates a balance between run-time simulation and compiled problem solving in diagnosis.