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PURPOSE OF REVIEW: To summarize the latest clinical developments in pharmacological interventions for primary cachexia. RECENT FINDINGS: New orexigenic interventions that interfere with the central regulation of food intake are expected to be derived from the group of melanocortin receptor antagonists and ghrelin-mimetic agents. Emerging are muscle agents, including ubiquitin-proteasome system inhibitors, antimyostatin drugs, dystrophin, and beta2-adrenergic agonists. Results from anabolic steroids and angiotensin-II inhibitors are awaited. Recent data support insulin tackling fat metabolism. Branched-chain amino acids, N-3 fatty acids and conjugated linoleic acid are nutritional supplements that show potential. Adenosine 5'-triphosphate expands to related compounds (including ubiquinone). No breakthrough has occurred with the use of anti-inflammatory agents. Moreover, nonsteroidal anti-inflammatory drugs and thalidomide merit definitive studies. Presently modern anticytokine treatments lack proof of broad effectiveness. Some NF-kappaB inhibitors hold early promise. Melatonin requires placebo-controlled trials before recommendations on clinical use. Oxidative stress probably contributes to muscle wasting. L-Carnitine and other antioxidants appear promising. Anticancer treatments designed as anticachexia interventions remain scarce. SUMMARY: A number of promising new agents are in development but are not yet regarded as standard of care. This void calls for well-designed, proof-of-concept studies followed by placebo-controlled, randomized trials.