As part of the effort to promote elimination of global health care disparities, this special supplement compiled 19 articles about practical diagnostic cytometry to recognize the recent achievements of laboratory scientists working in the shadow of the HIV/AIDS epidemics in resource limited settings. First, the clinical significance, diagnostic utility (as governed by international guidelines), and the historical perspectives of CD4+ T cell enumeration are reviewed. Then successful large-scale implementations of cost-effective CD4 counting are described for parts of Africa, USA, and the Caribbean. These activities are linked with both the training of personnel in fledgling laboratories as well as with external quality assessment implementations. Some of the more recent solutions related to pediatric CD4 testing using CD4% values are covered. Nevertheless, the need for further simplification and parsimony is still immense, and the potential solutions are catalogued in the articles written by experts operating in truly challenging rural environments. Cytometry is considered to be an expandable flexible technology for other assays beyond CD4 assessment, particularly within organized laboratory services in the Third World. These include haematological measurements, CD38/CD8 lymphocyte activation for viral load-related assessments, diagnosis of active tuberculosis and malaria, and bead-based serological assays for a variety of infectious diseases. The development and support of these emerging technologies by affluent countries is not entirely altruistic but is likely to be beneficial for both the Third and the First Worlds.