This literature review analyzes the results from studies applying conditioned medium and extracellular vesicles derived from the mesenchymal stem cell secretome to numerous disease states in animal and human in-vivo models. Information about the conditions treated and the observed benefits and side-effects of these therapeutics are discussed. Ongoing clinical trials applying conditioned medium and extracellular vesicles, recommended future research and limitations of cell-free strategies are addressed. Findings demonstrate that the mesenchymal stem cell secretome holds promise as an effective treatment for numerous disease states. This manuscript is a companion piece to “Part 1: Bioregenerative Applications of the Human Mesenchymal Stem Cell-Derived Secretome,” included in this issue, which contains background information about stem cells and mesenchymal stem cells, their limitations in-vivo and the advent of cell-free strategies as a viable alternative for disease treatment.