Erythrocytes (RBCs) are extremely sensitive cells, and although they do not have nuclei and mitochondria, are important health indicators. This is particularly true because, during inflammation, whether it is systemic or chronic, the haematological system is constantly exposed to circulating inflammatory mediators. RBCs have a highly specialized and organized membrane structure, which interacts and reacts to inflammatory molecule insults, and undergo programmed cell death, similar to apoptosis, known as eryptosis. Over the past years, eryptosis studies have focussed on determining if membrane changes have occurred, particularly whether a phosphatidylserine (PS) flip, Ca2+ leakage into the cell, changes to ceramide and cell shrinkage have occurred. Mostly, flow cytometry is used, but confocal microscopy and ultrastructural studies also confirm eryptosis. Here, we provide a comprehensive overview of eryptosis, where we revisit the biochemical process of the process, review all literature in PUBMED, that is shown under the search word, “eryptosis”, and also discuss current methodologies to determine the presence of eryptosis; included in the discussion of the methodologies, we discuss a pitfalls section for each method. This paper is therefore a comprehensive synopsis of current knowledge of eryptosis and discusses how RBCs may provide an essential in vivo cell model system to study not only inflammation in disease, but also track disease progression and treatment regimes.