Protein-lipid interfaces are among the most fundamental in biology. Yet applying conventional techniques to study the biophysical attributes of these systems is challenging and has left many unknowns. For example, what is the kinetic pathway and energy landscape experienced by a polypeptide chain when in close proximity to a fluid lipid bilayer? Here we review the experimental and theoretical progress we have made in addressing this question from a single molecule perspective. Some remaining impediments are also discussed.