Cultivar decline is a complex problem that merits intensive, multidisciplinary research efforts. Opinion surveys have consistently listed the sweetpotato virus disease (SPVD) complex and sweetpotato weevils as the major biological constraints to worldwide sweetpotato production. SPVD causes a precipitous decline in the performance of sweetpotato cultivars, reducing yields by as much as 90%. However, gradual, significant decline in yield and quality over several years also occurs in the absence of SPVD. There is growing evidence that cultivar decline may be caused by a variable complex of interacting factors, including mutations, viruses, and other pathogens. A recent international workshop on sweetpotato cultivar decline identified three groups of viruses as high priorities for research: potyviruses, criniviruses, and geminiviruses. The state of knowledge and needed research on identification, detection, geographic distribution, and economic importance of these groups of viruses in relation to sweetpotato is discussed. Bacteria and fungi also may have a role in cultivar decline, and recent research on Erwinia chrysanthemi is presented as an example.