Tissue engineering aims to improve the function of diseased or damaged organs by creating biological substitutes. Fabrication of multifunctional biomaterials that are able to mimic the mechanical properties, microstructure, cellular distribution, and molecular regulatory characteristics of the native extracellular matrix is essential in the engineering of functional tissues. Fibrous substrates have been recently emerged as promising scaffolding materials for making three-dimensional tissue constructs or delivering bioactive molecules. Many human tissues, such as musculoskeletal, cardiac, and connective tissues, possess a fibrillar architecture that offers interesting physical characteristics such as anisotropic mechanical properties. Thus, engineered fibrous constructs can potentially recreate these characteristics. In addition, using fibrous substrates for drug delivery offers the advantage of high surface to volume ratio, which allows for high drug loadings and the ability to overcome mass transfer limitations associated with other polymeric systems. Several groups including us have already proven their applications in connective and cardiovascular tissue engineering. In the first part of my talk, I will present our recent work on the fabrication of multifunctional fibrous scaffolds for the engineering of skeletal muscle tissue. I will discuss our bottom-up approach in which bioactive microfibers are fabricated from naturally-derived or synthetic materials and assembled into the final construct using textile methods or direct writing. The second part of my talk will be devoted to the use of advanced fibrous substrates that interface intimately with biological tissues in three dimensions. I will describe the application of these substrates in monitoring the physiochemical tissue properties and delivering drugs in a highly specific manner.