Bulk local tissue loss may be amenable to scaffold based therapies. Discrete areas can usually be filled in with composite scaffolds, which can then conform and integrate to host tissue. Many preclinical studies have demonstrated excellent efficiency in soft tissue reconstitution with acellular scaffolds, but tissue function and clinical translation have not been fully realized. Newer scaffolds carry growth factors and are structured to mimic host tissue architecture, to promote host tissue regeneration and scaffold ingrowth. Despite these considerable advances, the addition of cellular components, often in the form of stem or progenitor cells, can promote further return of tissue function that scaffolds alone. Inclusion of any cell types, however, results in increased costs, potential delay treatments, and vastly increased regulatory hurdles. Herein, we explore the benefits and concerns with the use of cells in scaffold-based tissue engineering, with a focus on tissue defects in muscle and clinical application.