Peptides are a major potential source of pharmacological agents and therapeutics but, unfortunately, their application is greatly limited by their poor ability to cross biological membranes. In our work we are using a combination computational and synthetic techniques to tackle this difficult problem. This presentation will describe our application of parallel cascade molecular dynamics simulations (PaCS) to model peptide permeation. It will also discuss our use of solid-phase library synthesis to design peptides that are both membrane permeable and bioactive.