Reducing body fat through conservative interventions is a frustrating process for obese people, hence the search for additional ways that can help patients persevere with long-term treatment procedures. Although data obtained from scientific studies do not allow for drawing clear conclusions about the use of sweeteners in the treatment of obesity, their appropriate use may prove beneficial. A review of the current literature was conducted to find the answers to the question of where such large discrepancies come from. It allowed for drawing the following conclusions: 1) Obese individuals may differ significantly in their sensitivity to sweet taste and even the sweeteners themselves; 2) The long-term effects of some sweeteners may neutralize the effect associated with short-term sweet appetite relief and even lead to the greater energy intake and/or utilization; 3) Natural sweeteners differ significantly from artificial sweeteners in terms of long-term effects; 4) The psychological effects of the sweeteners use (e.g., the acquiescence effect) may at least partially attenuate their inhibitory effects on food intake. Based on the review, guidance was developed for obesity practitioners and their patients regarding the use of sugar substitutes in fat reduction.