Sweetpotato (Ipomoea batatas) production is expanding faster than any other major food crop in sub-Saharan Africa (SSA), with about 13.4 million tons of roots from 3.2 million hectares in 2005. However, major constraints, including sweetpotato weevils (SPWs) and sweetpotato virus disease (SPVD) cause almost total crop loss on susceptible cultivars. This paper reviews examples where biotechnology in particular biofortification and genetic transformation could be used to improve sweetpotato for nutritional quality and food security. Expression of Cylas-active Bacillus thuringiensis (Bt) Cry proteins in sweetpotato could result in varieties potentially with field resistance against SPWs. Post transcriptional gene silencing (PTGS) mode of resistance to SPVD is promising. Quantitative trait loci (QTL) for dry-matter, starch, ß-carotene content, and yield have been identified in a hexaploid sweetpotato mapping population of ‘Tanzania’ (female, cream-colored flesh) x ‘Beauregard’ (female, orange-fleshed storage roots). Biotechnology approaches offer an attractive option of integrating some desired traits into farmer preferred sweetpotato cultivars in a more effective manner than conventional breeding.