Understanding the relationship between growth hormone (GH) structure (its molecular fragments) and function via interaction with single or multiple receptors is of particular importance in clinical diagnostics and physiologic biochemistry. Direct and indirect actions of GH are numerous ranging from carbohydrate and lipid metabolism to growth effects at muscle and vessels. To this end, we have focused on the influence of physical exercise on GH synthesis and release into the circulation. Physical exercise is a physiological condition to which GH multifunctionality is inextricably linked and is thus important physiologically and pathologically. This review describes the potential human GH fragments with respect to protein hormone multifunctionality and the molecular regions of potential action. The intent of the review is to highlight human GH fragments and hypothesize their potential physiologic role. GH fragmentation is also reviewed in relation to the effects of physical exercise and hormone multifunctionality.