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This paper presents the usefulness of weed species in semi-arid areas of Mpwapwa District, Central Tanzania. As crop production systems in these areas are often impacted by unreliable rainfall, frequent drought, and low soil fertility, smallholder farmers have developed different strategies to ensure that their livelihood is sustained. One of these strategies is the use of weed species for different purposes. A field inventory conducted in 36 smallholder farmers' fields in the case study area during the 2006/2007 cropping season identified a total of 63 weed species from 26 plant families. Usefulness of identified weed species in these areas was determined through focus group discussions with community representatives. Out of 63 weed species presented during these meetings, nine species were indicated as the most useful weed species in those communities. Pairwise ranking indicated Cleome hirta (mhirile) to be the most important species. Others in order of importance were: Amaranthus graecizans (mfwene), Bidens lineoriloba (mphangalale), Bidens pilosa (mpwimbwiza), Dactyloctenium aegyptium (ihungo), Launaea cornuta (sunga), Heteropogon contortus (sigi), Tragus berteronianus (namata), and Trichodesma zeylanicum (nyawaje). These species were mentioned to be mainly used as vegetable, medicine, food, fodder, and thatching materials. Weed species used as food have been mentioned to help people during period of droughts. Medicinal weed species were also mentioned to be useful in the area. Ailments mentioned that can be treated by selected species include malaria, painful menstruation, extended menstruation cycle, and stomach ache in men (ngiri). These species are also said to reduce blood flow during circumcision. The majority of women in the area were the ones involved in harvesting, preparation, and selling the useful weed species in the visited markets. The main conclusion drawn from this study is that, although weed species are regarded as unwanted plant species in crop production, they still play a vital role in food security and for the health of different people in marginal areas.