Control of fecal–orally transmitted pathogens is inadequate in many developing countries, in particular, in sub-Saharan Africa. Acquired resistance to antimicrobial drugs is becoming more prevalent among Vibrio cholerae, Salmonella enteritidis, diarrheagenic Escherichia coli, and other pathogens in this region. The poor, who experience most of the infections caused by these organisms, bear the brunt of extended illness and exacerbated proportion of deaths brought about by resistance. Improved antimicrobial drug stewardship is an often cited, but inadequately implemented, intervention for resistance control. Resistance containment also requires improvements in infectious disease control, access to and quality assurance of antimicrobial agents, as well as diagnostic facilities. Structural improvements along these lines will also enhance disease prevention and control as well as rational antimicrobial drug use. Additionally, more research is needed to identify low-cost, high-impact interventions for resistance control.