Soft tissue deficits resulting from congenital deformities, aging, trauma, or post-surgical tissue loss are debilitating problems that can be challenging to reconstruct. However, the introduction of autologous fat transfer has revolutionized the field of soft tissue reconstruction and augmentation. Its abundance, ease of harvest, and immunocompatibility have made autologous fat an ideal candidate to correct contour deformities throughout the body. Nevertheless, there has been substantial inconsistency in reported outcomes due to variable rates of resorption. More recently, progress has been made in understanding the molecular mechanisms that govern adipogenesis and adipocyte survival. Furthermore, investigations continue on the large pool of resident adipose-derived stromal cells (ASCs) within fat, which may serve as a potential resource for tissue engineering. This review provides an overview on our current understanding of autologous fat grafting, adipose biology, adipose tissue engineering, and the potential role ASCs may play in modifying the local tissue environment to enhance fat transfer outcomes.