-Abstract- Integral membrane proteins play pivotal roles in various cellular functions such as signal transduction and material transfer across membrane barrier. These bio-macromolecules are insoluble in aqueous media as a result of incompatibility between the hydrophilic property of the solvent molecules and the hydrophobic nature of membrane protein surfaces, normally associated with lipid membranes. Amphipathic compounds, called detergents, are necessary for extraction of these macromolecules from the native membranes and their maintenance in solution. However, membrane proteins encapsulated by conventional agents tend to denature or aggregate. Thus, keeping the native structures of membrane proteins in detergent micelles is a major bottleneck in membrane protein study, suggesting that novel agents with enhanced efficacy are necessary to beyond the bottleneck. Detergent structure-property relationships provide keys in this effort because such information serves as guidelines in design of novel amphiphiles. In the current presentation, I will focus on some of these relationships we have recently found, based on several studies about novel amphiphiles. These detergent structure-property relationships will facilitate rational design of novel amphipathic agents, thereby leading to advances in membrane protein research.