Antimicrobial resistance has recently and rapidly escalated to the point where microbes are overcoming infectious disease therapies faster than humans are developing them. The African resistance epidemic is relatively under documented because of insufficient surveillance. Resistance in the pathogens that cause AIDS, malaria and tuberculosis is of paramount concern, but as they are expensive to culture, surveillance is only conducted at sentinel centers, if at all. In studies using more readily cultivatable indicator bacteria, we have observed an exceptionally steep and steady increase in resistance to commonly used, cheap, broad-spectrum antibacterial drugs in Nigeria and other parts of sub-Saharan Africa. Urbanization demonstrably contributes to the rising prevalence of resistant organisms and other likely contributors include unregulated antimicrobial misuse, diagnostic insufficiency and poor quality drugs. As spelled out in the World Health Organization’s recently issued strategy for resistance containment, antimicrobial resistance must be addressed though a multifaceted approach. Many developing countries are presently faced with difficulties in prioritization of WHO-recommended interventions. Recent evidence suggests that a number of validated infectious disease control interventions additionally contribute to stemming resistance. Examples include Short-course Directly Observed Therapy (DOTS) for tuberculosis, the Integrated Management of Childhood Diseases (IMCI) initiative as well as pneuomococcal vaccination. Drug use policies, particularly if implemented at national and regional levels and sensitive to unofficial as well as official markets also show promise for resistance control.