An important goal of structural biochemistry is the reduction of complex molecules to small functional units that are amenable to high-resolution structural analysis and rapid modification. The dissection of multidomain proteins into small synthetic conformationally restricted components is an important step in the design of low molecular weight nonpeptides that mimic the activity of the native protein. Mimetics of critical functional domains might possess beneficial properties in comparison to the intact proteinaceous species with regard to specificity and therapeutic potential, and are valuable probes for the study of molecular recognition events. 1. Introduction 2. Peptidomimetic Discovery Strategies 3. The Secondary Structure Approach 4. First Generation Reverse Turn Mimetics 5. The Second Generation 6. Third Generation Mimetics 7. Conclusions