The electrospinning method has been widely used to produce nano/micro fibers for various applications. As a drug delivery system, electrospun fibers display many advantages such as controlled drug delivery kinetics and the ability to deliver drugs locally. A drug delivery system improves delivery efficiency and reduces possible toxic effects. In particular, multiaxial fibers consisting of two or more fluid components have drawn attention for the simultaneous administration of multiple therapeutic agents for sustained delivery and effective treatment. This review discusses recently studied multi-compartment electrospun fibers, including side-by-side (Janus) and axially symmetric fibers - coaxial and triaxial - from the perspective of multi-drug incorporation. It begins with an overview of conventional uniaxial single-fluid electrospinning methods for drug delivery applications, then highlights the advantages of multi-compartment fibers for multi-substance loading/delivery and the advances in triaxial fibers that seem to be promising from the perspective of challenges for dressings and tissue regeneration. Furthermore, drug release mechanisms and kinetics are discussed in the controlled delivery of multiple therapeutics in fibers. In the conclusion, current biomedical applications of multi-drug delivery systems in selected applications and future perspectives are presented.