Purpose of Review: There is a common perception among the public that yo-yo dieting, defined as repeated cycles of weight loss followed by weight regain, results in accumulation of fat in the body and lower metabolic rate, thus hindering subsequent attempts to lose weight. We evaluated the effects of weight-cycling on body weight and body mass index (BMI), body composition including fat mass (FM) and lean body mass (LBM), and resting metabolic rate (RMR), by systematically reviewing existing scientific literature. Recent Findings: Twenty-three cross-sectional and cohort studies (including subjects with a history of weight-cycling compared to those without such history) and interventional studies (evaluating physiological effects during one or more cycles of weight loss and regain) were identified, conducted in generally healthy adults across various age groups, races, and both genders, who had normal weight, overweight, or obesity. Eighteen studies investigated the association between weight-cycling and body weight or BMI, and thirteen of them found no significant association. Fifteen out of twenty studies also found no increase in FM, and none of eighteen studies found a decrease in LBM. Twelve out of fourteen studies reported no adverse changes in RMR either. Summary: The overwhelming majority of evidence suggests that weight-cycling (yo-yo effect) is not associated with any adverse effects in body weight, body composition, and metabolic rate. Accordingly, healthy individuals who struggle with overweight or obesity should not be discouraged from repeated attempts to lose the excess weight.