Although obesity is associated with increased mortality rate and short-term weight loss improves risk factors for mortality, it has not been convincingly shown that weight loss among obese people results in reduced mortality rate. When considering the human literature, it has been pointed out that weight loss is often a sign of illness and that investigators therefore need to separate intentional from unintentional weight loss. It has generally been assumed that among people who state that they do not intend to lose weight, weight change subsequently observed is unintentional. Among such people, weight loss has been consistently associated with increased mortality rate. Complementarily, it has generally been assumed that among people who state that they do intend to lose weight, weight change subsequently observed is intentional. In these people who are intending to lose weight, some studies show apparent benefits of weight loss, some are neutral, and some show deleterious effects. The overall conclusion that some reviewers have drawn from this literature is that intentional weight loss (IWL) is at best not beneficial and may even be harmful with respect to mortality rate. We believe that this conclusion is drawn by inappropriately conflating weight loss (or more generally weight change) among people intending to lose weight with IWL (or change). Herein, under certain assumptions, we: (1) show that the association between mortality rate and weight loss among people intending to lose weight and between mortality rate and IWL are two different things; (2) show that the association between IWL and mortality rate is an inherently unobservable entity; (3) derive a method for estimating the plausible range of true effect of IWL on mortality rate if one is willing to make a number of restrictive, but perhaps reasonable assumptions; and (4) illustrate the method by application to a data set involving middle-age onset calorie restriction in mice. Copyright © 2005 John Wiley & Sons, Ltd.