Electrospinning is a versatile technique to produce micron or nano sized fibers using synthetic or bio polymers. The unique structural characteristic of the electrospun mats (ESM) which mimics extracellular matrix (ECM) found influential in regenerative tissue engineering application. ESM with different morphologies or ESM functionalizing with specific growth factors creates a favorable microenvironment for the stem cell attachment, proliferation and differentiation. Fiber size, alignment and mechanical properties affect also the cell adhesion and gene expression. Hence, the effect of ESM physical properties on stem cell differentiation for neural, bone, cartilage, ocular and heart tissue regeneration will be reviewed and summarized. Electrospun fibers having high surface area to volume ratio present several advantages for drug/biomolecule delivery. Indeed, controlling the release of drugs/biomolecules is essential for sustained delivery application. Various possibilities to control the release of hydrophilic or hydrophobic drug from the ESM and different electrospinning methods such as emulsion electrospinning and coaxial electrospinning for drug/biomolecule loading are summarized in this review.