In spite of the recent developments in structural biology, membrane proteins continue to pose tremendous challenges to most biophysical techniques. A major area of research in my group has been focused on the development of NMR techniques to study the dynamic structural interactions between membrane bound proteins that are implicated in the pathology of many diseases. My lecture will focus on the approaches to overcome the major challenges related two such examples. Strategies to study atomic-resolution structure and dynamics of membrane proteins, and the dynamic molecular events enabling the enzymatic function of cytochrome P450 will be presented. Protein misfolding and amyloid aggregation, structures of early amyloid intermediates and mechanisms of amyloid induced membrane disruption related to Alzheimer’s disease and type-2 diabetes will also be discussed.