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Nanofibers obtained using electrospinning technique are being used since ages especially in fields of textile industry, sensors, filters, protective clothing and tissue engineering. Their use as drug delivery system is an emerging platform in the field of pharmaceuticals and now-a-days formulation scientists are paying great attention to the technology due to several advantages prime being easy modulation of drug release profile depending upon the properties of polymer/polymeric blends/other materials used. Although there are several reports citing the use of antibiotics-loaded nanofibers as wound dressing materials and as antimicrobial therapy in periodontics; still there is a good scope of expanding the horizon for its application in newer ailments. This article reviews various aspects related to loading and release of drug as such or in nano-particulate form to polymeric nanofibers by taking critical process parameters (CPPs) for electrospinning and critical material attributes (CMAs) into account. Commercially available products and electrospinning technologies are described in brief along with some of the patents related to their use as drug delivery systems. The main focus of this review is applicability of drug/drug nanoparticle loaded nanofibers in the management of diseases/disorders related to the brain, eye, ear, cardiovascular system, lungs and oral cavity. Use in diseases with higher mortality rates like diabetes, Acquired immunodeficiency syndrome (AIDS) and cancer is also described in brief.