One issue was definitely not enough! We are prompted to be active, and we are told that exercise is medicine. Indeed, exercise is great medicine: it keeps at bay metabolic conditions associated with sedentarism, and exerts a favorable effect on our mental health. Some of us are born exercisers, some become so, some drift from being great athletes in youth to a life in an armchair, and some discover exercise later in life. Many of us are competitive, and we often compete against ourselves, never to win. For all of us, however, middle-age looms, and osteoarthritis (OA) may become a major issue: in the West, up to 20% of individuals close to retirement age suffer from it, and their life can be ruined. It is not surprising, therefore, that so much interest is placed on how to prevent, diagnose, manage, “cure” OA: a never-ending battle, with no end in sight. As physicians, we would like to know why some of our patients have developed OA, and others are spared. Why some present little evidence of joint degeneration, and are crippled with pain. Above all, we want to make our patients better. The first part of this series produced a great set of evidence-based systematic reviews of the literature on several epidemiological aspects of OA and middle age sports practice. In a natural evolution, this second issue of Sports Medicine and Arthroscopic Review continues along those lines, and dwells in some aspects of biology and regenerative medicine, examining, for example, how drugs can be delivered in a novel fashion, and whether allogeneic tissues can be used to regenerate our battered articular cartilage. In this field, imagination has to be married with high-level science to progress our clinical knowledge. Eventually, exercise is medicine, and, as with all medications, too much is never too good. The spectre of overdosing must be corrected by our regenerative capabilities. Hopefully, this issue will help pave the way. On the Cover: Role of cytokines in mediating the communication between immune cells. In color, the molecules upregulated in platelet-rich plasma compared with platelet-poor plasma. Sports Med Arthrosc Rev. 2022;30:141–146.