General System Theory was proposed in the post-war period as a unifying framework for interdisciplinary science based on the idea that systems have a set of similar properties and characteristics regardless of discipline. General System Theory laid the foundations for talking about things in terms of systems, many of its terms are now embedded in everyday language and it underpins a broad range of systems approaches and systems thinking. This chapter will describe the key elements of the original General System Theory (GST) including control, feedback, emergence, holism and the notion of a hierarchy of systems within systems. It will review the origin, content and foundational role of systems theory in biology, medicine, computer science, organizational theory and its central contribution to health informatics. In recent years, healthcare organizations have been encouraged to see themselves within the context of learning health systems (LHS) and to use emerging big data analytics techniques such as process mining to develop better, integrated and personalized pathways of care for patients. We use GST to reflect on these emerging approaches through a discussion and case study on recent work in urgent and emergency care. Our aim is to trace the influence of GST through emerging LHS ideas and use the framework of GST to reflect on the opportunities and limitations of our process mining approach. In particular, we will reflect on how GST can explain successes and failure in the application of process mining to care pathways and the challenges and opportunities ahead.