Adipose tissue mesenchymal stem cells (AD-MSC or ADSC) are multipotent cells that do not show immune rejection. In this work, we analyze the route of administration and its possible differentiation into specific lineages of adipogenic, chondrogenic, osteogenic, myogenic, or neurogenic phenotypes. Transplanted cells induced tissue repair by inducing angiogenic, anti-inflammatory, and immunomodulatory effects (IDO, PG-2, nitric oxide, and some cytokine signaling). The ADSC exert these tissue repair processes through the release of chemokines and growth factors in a paracrine manner. Other fat-derived stem cells such as perivascular adipose tissue cells (PVAT) and muse cells induced reparative effects. Cell-free therapy using stromal vascular fraction (SVF) or the use of exosomes releasing miRNAs and cytokines also confirmed their safety and efficacy in vitro. Several published preclinical and clinical trials with AD-MSC confirmed their beneficial effects to repair and prevent chronic-degenerative pathologies. In this chapter, we review AD-MSC-based therapies that have used preclinical rodent models of disease for cartilage repair, regeneration of the peripheral and central nervous system, dental bone, myocardium, and liver, and in the treatment of perianal fistula in Chron’s disease, and in wound and skin fibrosis repair. In addition, this work also includes clinical studies with AD-MSC or other fat-derived stem cells in patients with various pathologies.