The interest of using electrospun scaffolds for soft and interface tissue engineering applications is continuously increasing. The morphology of electrospun fibers resembles the native extra cellular matrix fibrillary structure. Most of recently published work has focused on the so called “green electrospinning” and the use of benign, e.g. health and environment friendly, solvents for electrospinning. The reasons behind this trend could be identified in the need to prevent proteins and biomolecules denaturation, which has been reported for most of the “standard” solvents used conventionally in electrospinning, as well as the need for additional neutralization post-processing to eliminate solvent residuals from the obtained scaffolds. In this work, benign solvents, like acetic acid and formic acid were used for the fabrication of a variety of synthetic polymer fibers and their blends with natural polymers like gelatin, chitosan and silk. The results obtained from morphological, chemical and mechanical characterization of the obtained fibers demonstrated comparable properties to fibers obtained from “standard” (toxic) solvents and confirmed the suitability of the novel fibrous scaffolds for applications in soft and interface tissue engineering. The versatility of the use of benign solvents was also checked during the functionalization process of electrospun mats. Remaining challenges for the universal use of such benign solvents with a variety of polymers, polymer-inorganic filler composites and polymer blends will be discussed.