In the review we analyzed short history of the establishment of a novel hematological parameter for systemic inflammation and stress coined as a neutrophil to lymphocyte ratio (NLR). Today NLR is widely used across almost all medical disciplines as a reliable and easy available marker of immune response to various infectious and non-infectious stimuli. We analyzed the immunological and biological aspects of dynamic changes of neutrophil granulocytes and lymphocytes in circulating blood during endocrine stress, dysbalance of autonomic nervous system and systemic inflammation. NLR reflects online dynamic relationship between innate (neutrophils) and adaptive cellular immune response (lymphocytes) during illness and various pathological states. NLR is influenced by many conditions including age, rice, medication, chronic disease like coronary heart disease, stroke, diabetes, obesity, psychiatric diagnosis, cancer of solid organs, anemia and stress. A normal range of NLR is between 1-2, the values higher than 3.0 and below 0.7 in adults are pathological. NLR in a grey zone between 2.3-3.0 may serve as early warning of pathological state or process such like cancer, atherosclerosis, infection, inflammation, psychiatric disorders and stress. NLR is used as a reliable and cheap marker of ongoing cancer-related inflammation and a valid indicator of prognosis of solid tumors. Majority of meta-analyses have explored the prognostic value of NLR in various solid tumors and have found out the cut-off value of NLR above 3.0 (IQR 2.5-5.0). We summarized its privilege in oncology: NLR may be used for stratification of cancer, correlates with the tumor size, stage of tumors, metastatic potential and lymphatic invasion. NLR has independent prognostic role regarding overall, cancer free and cancer-specific survival. It is useful for monitoring oncological therapy, including biological and immune check point inhibitors treatment. NLR is a very sensitive indicator of infection, inflammation and sepsis, validated in numerous studies. Clinical research confirmed the sensitivity of NLR for diagnosis/stratification of systemic infection, sepsis, bacteremia as well as its robust predictive and prognostic value. NLR should be investigated daily, and follow-up its absolute values and dynamic course in acute disease or critical illness. The severity of critical illness, the level of stress and serious inflammation is expressed by dramatic increasing of NLR values above 11 ≥ 17, or even higher than 30. Improving the clinical course of sepsis, critical illness, lower risk of mortality are associated with decline of NLR values below 7. NLR is helpful in differentiating more severe disease versus milder one. NLR is cheap, simple, fast responding and easy available parameter of stress and inflammation with high sensitivity and low specificity, it should be used routinely in emergency departments, ICUs, in acute medicine including surgery, orthopedics, traumatology, cardiology, neurology, psychiatry and even oncology. Dynamic changes of NLR precede the clinical state for several hours and may warn clinicians about the ongoing pathological process early. NLR is a novel perspective marker of cellular immune activation, a valid index of stress and systemic inflammation, which open a new dimension for clinical medicine, for better understanding of the biology of inflammation, coupling and antagonism between innate and adaptive immunity and its clinical consequences for health and disease (Tab. 8, Fig. 3, Ref. 151). Keywords: neutrophil-to-lymphocyte ratio, systemic inflammation, immune-inflammatory response, endocrinne stress.