There is a need to introduce cytometry into areas of the globe that have remained virtually untouched by modern laboratory medicine. With the demand to carry out tests on 100,000 s of individuals requiring antiretroviral therapy (ART), flow cytometry must remain simple and cost-effective - while being sustainable and industry supported as well as proven by quality assessment (QA). This outlook is referred to as "smart flow cytometry" (S-FC). There are five main areas where the power of S-FC is demonstrated. These are: (i) the use of CD45 to assist precise cell counting in blood and tissue samples; (ii) the primary CD4 gating to count CD4+ T cells in patients waiting for ART, including the combination (i) and (ii) in the panleucogating (PLG) protocol; (iii) monitoring of human immunodeficiency virus (HIV+) patients during ART by the decreasing levels of lymphocyte activation in a CD8/CD38 test - leading to economies of viral-load assays; (iv) in tuberculosis and HIV-TB coinfections the use of TB-antigen-stimulated cytokine-synthetic CD4+ T cells to identify active disease; and (v) the utilization of "minimal residual disease (MRD)-Lite" technology in patients 19 days after the start of antileukemic therapy to detect MRD. These methods of S-FC have been successfully introduced in "resource-restricted" countries with international and local QA.