This study was conducted to document and evaluate knowledge on medicinal plant use by Sheko ethnic group in Southwest Ethiopia. Interviews and ranking exercises were the main methods employed to collect the ethnobotanical data. Fidelity level (FL) values were calculated for claimed Sheko medicinal plants to estimate their healing potentials. Seventy-one Sheko medicinal plants were reported, the majority of which were used to treat skin and gastro-intestinal ailments. Ocimum lamiifolium, Phytolacca dodecandra, Amaranthus dubius and Amaranthus graecizans were the medicinal plants assigned with the highest FL values, a possible indication of their better healing potential. The majority of Sheko medicinal plants were found to be herbs, and leaf was the most preferred plant part in remedy preparations. The study indicated that men, older people and illiterate ones had better knowledge of medicinal plants use as compared to women, younger people and literate ones, respectively. The study showed that the Sheko people have rich knowledge of medicinal plant use. This knowledge is however, currently threatened mainly due to acculturation. Awareness should thus be created among Sheko community by concerned bodies regarding the usefulness of their medical practice. The efficacy and safety of the claimed medicinal plants need to be evaluated before recommending them for a wider use with priority given to those with high fidelity level values. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.