Traumatic injuries to the musculoskeletal system are common events and volumetric muscle loss (VML) is no longer a rare occurrence. Surgical intervention is typically the only option for restoration of partial function. Surgical intervention for VML however does not regenerate the lost tissue and typically results in alterations of both the anatomy and biomechanics at the site of injury. Non-traditional approaches to the restoration of functional musculoskeletal tissue, including those provided by tissue engineering and regenerative medicine strategies, become viable alternative therapies when the expected outcome is bleak. One such strategy involves the delivery of constructive cues and modulation of the micro-environmental niche via biologic scaffold materials. These materials ideally retain the native structure and composition of the extracellular matrix of the tissue from which they are derived. Some of the recent advances in the use of biologic scaffolds to target key stages of the musculotendinous repair process and promote the restoration of functional tissue are described herein.