Chronic diseases are both common and deadly. Due to the limitations of conventional therapies for chronic diseases such as advanced heart failure and diabetes mellitus, recent interest has been directed towards regenerative medicine. In this review, we examine the history of regenerative biology and emphasize the dynamic and multidisciplinary growth of this field. We highlight the spectrum of adult tissues that have a remarkable regenerative capacity (i.e., skeletal muscle) versus those that have a more limited regenerative capacity (i.e., heart). We further emphasize the use of relevant contemporary models for the study of regenerative biology (i.e., pancreatic regeneration), which highlight both the challenges for this field of study and the potential for regenerative medicine, including the use of cell-based strategies, to revolutionize medical therapies for chronic diseases.