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Stem cells have been long looked at as possible therapeutic vehicles for different health related problems. Among the different existing stem cell populations, Adipose- derived Stem Cells (ASCs) have been gathering attention in the last 10 years. When compared to other stem cells populations and sources, ASCs can be easily isolated while providing simultaneously higher yields upon the processing of adipose tissue. Similar to other stem cell populations, it was initially thought that the main potential of ASCs for regenerative medicine approaches was intimately related to their differentiation capability. Although this is true, there has been an increasing body of literature describing the trophic effects of ASCs on the protection, survival and differentiation of variety of endogenous cells/tissues. Moreover, they have also shown to possess an immunomodulatory character. This effect is closely related to the ASCs' secretome and the soluble factors found within it. Molecules such as hepatocyte growth factor (HGF), granulocyte and macrophage colony stimulating factors, interleukins (ILs) 6, 7, 8 and 11, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), adipokines and others have been identified within the ASCs' secretome. Due to its importance regarding future applications for the field of regenerative medicine, we aim, in the present review, to make a comprehensive analysis of the literature relating to the ASCs' secretome and its relevance to the immune and central nervous system, vascularization and cardiac regeneration. The concluding section will highlight some of the major challenges that remain before ASCs can be used for future clinical applications.