Objective To review recent clinical literatures on the effectiveness of HMB supplementation in pathological conditions. Methods Utilizing electronic online database search using the keyword HMB, then screened, compared and summarized the results of HMB supplementation. Results β-hydroxy-β-methylbutyrate is a metabolite of the essential amino acid leucine. Plenty of researches show that HMB may have the effect in preventing muscle wasting and increasing muscle mass, and has been widely used in sports and body building. Many diseases, such as severe trauma, cancer, AIDS, the elderly muscle atrophy may lead to muscle wasting. Therefore, HMB is also used in clinical treatment for muscle wasting in the past few years. Conclusions Although there are discrepancies among the results of different studies, HMB supplementation has been shown its increase effect on lean body mass in the most of literatures. Consequently, HMB supplementation attenuates muscle wasting and reduces the risk of poor prognosis. It may due to the complex metabolism of HMB.