Amphiphilic nanostructures provide unique environments for molecules that are incompatible with the solvent to be sequestered within their interior. These internal environments provide opportunities for concentrating an analyte or transducer molecule for detection, and the functional groups within the amphiphiles provide an opportunity for incorporating specificity or selectivity toward analytes. In this review, we discuss ways in which amphiphilic assemblies can be used to detect peptides and proteins with a particular emphasis on facially amphiphilic polymers and dendrimers.