Data from experiments on animals and humans have supported the development of computer models that predict human response to various combinations of the three main heat stress factors work, clothing, and environment. However, recent application of such models shows that the validity of their output is limited in part by the need to represent more faithfully the interactions among the primary heat stress factors and certain physiological variables. Examples of such interactions include the weight and stiffness of protective outfits increasing the metabolic cost of a task, profuse sweating that wets clothing and alters its heat transfer characteristics, task-related movements altering air exchange rates through clothing, individual aerobic capacity affecting thermoregulatory response to a given metabolic load, and sweat retention in clothing raising skin wettedness and possibly inducing sweat suppression. This paper reviews recent research in these areas and identifies certain areas where further data are needed.