Poor aqueous solubility of both, existing drug molecules and those which are currently in the developmental stage, have posed a great challenge to pharmaceutical scientists because they often exhibit poor dissolution behavior and subsequent poor and erratic bioavailability. This has triggered extensive research to explore nanotechnology-based technology platforms for possible rescue. Recently, nanofibers have been exploited widely for diverse biomedical applications including for drug delivery. Electrospun nanofibers are capable of preserving the homogeneously loaded therapeutic agents in amorphous state potentialy impairing devitrification. The present review aims at providing an overview of the various key factors that affect the electrospinning process and characteristics of the nanofibers while fabrication of drug loaded nanofibers for poorly soluble drug candidates. The review explores various methodological advancements in the electrospinning process and set-ups for production scale-up. The various types of electrospun nanofibers (like simple matrix, core-sheath, Janus, and inclusion complex nanofibers) that have been exploited for the delivery of poorly soluble drugs are also critically assessed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.