Over the past few decades, the rapid evolution of computing, communication, and sensor technologies has brought about the proliferation of asynchronous distributed dynamic systems, mostly artificially constructed and often highly complex, such as intelligent transportation systems, computer and communication networks, automated manufacturing systems, air traffic control systems, and distributed software systems. In such man-made systems, most activities are governed by operational rules, and their dynamics are therefore characterized by occurrences of discrete events. Modeling and analyzing such systems are far beyond the scope of traditional system theory that is built on differential/difference equations. In this talk, I will first present modeling tools that are appropriate for asynchronous distributed systems, and then focus on specific estimation and diagnosis problems to demonstrate techniques that can be used for system analysis.