Developing effective, affordable, and sustainable delivery strategies for the isolated low-income populations that stand to gain the most from micronutrient interventions has proven difficult. We discuss our experience with implementation of zinc as treatment for diarrhea in children less than 5 y of age over the course of 3 operational research studies in rural Sikasso Region, Mali, West Africa. The initial formative research study highlighted how malaria affects perceptions of diarrhea and its causes and that malaria and diarrhea are not necessarily viewed as distinct conditions. The second-phase pilot introduction demonstrated that, in introducing zinc treatment in malaria-endemic regions, it is especially important that both community- and facility-level providers be trained to manage sick children presenting with multiple symptoms. The third-phase study on large-scale implementation detected that the experience with implementation of new treatments for malaria is distinct from that of diarrhea. To some extent zinc treatment is the solution to a problem that communities may not recognize at all. Interventions to improve case management of sick children must be integrated across diseases and nutritional problems at both the facility and community levels. Operational research can identify points where integration should occur and how it should be carried out. Programs targeting single diseases or single nutritional problems can have a variety of deleterious effects on health systems, no matter how well they are planned.