Anorexia, defined as the loss of the desire to eat, is relatively common in hemodialysis (HD) patients, occurring in one-third of cases. The pathogenesis is essentially unknown. It has been proposed that uremic toxins as middle molecules, inflammation, altered amino-acid pattern, leptin, ghrelin, and neuropeptide Y are involved. Anorexia reduces oral energy and protein intakes, thus contributing to the development of malnutrition and cachexia. Unquestionably, it contributes to poor quality of life. The clinical relevance of anorexia as an independent prognostic factor in HD patients is a matter of debated issue. The treatment of this debilitating condition is based on a therapeutic strategy which may include daily dialysis sessions and nutritional counseling. Normalization of plasma branched-chain amino acids through branched-chain amino acids supplementation may decrease anorexia and improve energy and protein intake. The role of megestrol acetate as appetite stimulant needs to be validated through adequate randomized trials. Subcutaneous ghrelin administration and melanocortin-receptor antagonists appear promising therapeutic interventions.