In the present work, a systematic study of the release kinetics of two embedded model drugs (one completely water soluble and one partially water soluble) from hydrophilic and hydrophobic nanofiber mats was conducted. Fluorescent dye Rhodamine B was used as a model hydrophilic drug in controlled release experiments after it was encapsulated in solution-blown soy-protein-containing hydrophilic nanofibers as well as in At electrospun hydrophobic poly(ethylene terephthalate) (PET)-containing nanofibers. Vitamin B-2 (riboflavin), a partially water-soluble model drug, was also encapsulated in hydrophobic PET-containing nanofiber mats, and its release kinetics was studied. The nanofiber mats were submerged in water, and the amount of drug released was tracked by fluorescence intensity. It was found that the release process saturates well below 100% release of the embedded compound. This is attributed to the fact that desorption is the limiting process in the release from biopolymer-containing nanofibers similar to the previously reported release from petroleum-derived polymer nanofibers. Release from monolithic as well as core-shell nanofibers was studied in the present work. Moreover, to facilitate the release and ultimately to approach 100% release, we also incorporated porogens, for example, poly(ethylene glycol), PEG. It was also found that the release rate can be controlled by the porogen choice in nanofibers. The effect of nanocracks created by leaching porogens on drug release was studied experimentally and evaluated theoretically, and the physical parameters characterizing the release process were established. The objective of the present work is a detailed experimental and theoretical investigation of controlled drug release from nanofibers facilitated by the presence of porogens. The novelty of this work is in forming nanofibers containing biodegradable and biocompatible soy proteins to facilitate controlled drug release as well as in measuring detailed quantitative characteristics of the desorption processes responsible for release of the model substance (fluorescent dye) and the vitamin (riboflavin) in the presence of porogens.