Immune organ failure is frequent in critical illness independent of its cause and has been acknowledged for a long time. Most patients admitted to the ICU, whether featuring infection, trauma, or other tissue injury, have high levels of alarmins expression in tissues or systemically which then activate innate and adaptive responses. Although necessary, this response is frequently maladaptive and leads to organ dysfunction. In addition, the counter-response aiming to restore homeostasis and repair injury can also be detrimental and contribute to persistent chronic illness. Despite intensive research on this topic in the last 40 years, the immune system is not routinely monitored in critical care units. In this narrative review we will first discuss the inflammatory response after acute illness and the players of maladaptive response, focusing on neutrophils, monocytes, and T cells. We will then go through commonly used biomarkers, like C-reactive protein, procalcitonin and pancreatic stone protein (PSP) and what they monitor. Next, we will discuss the strengths and limitations of flow cytometry and related techniques as an essential tool for more in-depth immune monitoring and end with a presentation of the most promising cell associated markers, namely HLA-DR expression on monocytes, neutrophil expression of CD64 and PD-1 expression on T cells. In sum, immune monitoring critically ill patients is a forgotten and missing piece in the monitoring capacity of intensive care units. New technology, including bed-side equipment and in deep cell phenotyping using emerging multiplexing techniques will likely allow the definition of endotypes and a more personalized care in the future.