THIS issue of Cytometry contains three reviews that further celebrate the longstanding, intense, and happy marriage between Cytometry and Immunology, as highlighted recently during the XV International Congress of Immunology, held in Milan, Italy, August 22–27, 2013. Scanning the scientific contributions of the Conference reveals that cytometric technology was used in the vast majority of abstracts and presentations. In other words, very few scientists did not switch on one or more lasers! It is obvious, that nowadays very few studies in the field of Immunology are possible without techniques based upon single cell analysis. In our previous editorial (1), we have underlined how the creation of monoclonal antibodies (mAbs) (2) and their conjugation with a variety of fluorochromes has been an unprecedented motivation and help (that we defined as the “official exchange of rings”) for the development of an instrument, i.e., the flow cytometer, that only a few years before had been built and commercialized for measuring cellular DNA by fluorescent intercalating dyes such as ethidium bromide. Fluorescent mAbs detecting the CD4 molecule became then crucial not only for the identification of the alterations occurring in patients infected by the human immunodeficiency virus (HIV), but also to follow the efficacy of antiretroviral therapy, as more than 3 decades of studies teach us (3). The clinical use of mAbs and flow cytometry had finally led to the development of cytometers that are much easier to use than the original instruments they derive from. They are user friendly and can have affordable prices, and they have become workhorses for the immunologist. Though still today, the preparation of cells and the evaluation of cytometric data remain challenges. But the field is moving and enchanting new developments become available in cytometry. This adds some spice and excitement to the relationship. In the aftermath of the XVth International Congress on Immunology, we thought it is worthwhile to give some feedback on exciting developments in immunology to the Cytometry community and dedicate some space to the discussion of cutting-edge immunology in the August issue of Cytometry, the pre-eminent journal in the field, and some more space in this issue. Here, immunologists with longstanding cytometric experience provide three reviews that address the impact of state-of-the-art cytometry on the understanding of how lymphocytes function and how they are instructed and imprinted for function. Understanding these mechanisms is key to understand the role of the immune system in protection, infection, chronic inflammatory diseases, and aging. Cosmi et al. discuss novel aspects related to CD41 T lymphocytes, which are crucial cells for the regulation of immune responses and the development of immunological memory. CD41 T cells are a very heterogeneous population, and cytometry has and still is playing a key role in deciphering this heterogeneity and understanding its impact on immune reactions, protective, and pathogenic ones. The importance of Th1 and Th2 lymphocytes are discussed, along with other populations that have been phenotypically thoroughly characterized, such as the Th17 subset, but also less well accepted subtypes, like Th22, Th9, and T follicular helper (Tfh) lymphocytes. In particular, this review discusses the