Cancer poses a major public health problem all over the world and it is the second leading cause of death after cardiovascular disease. The incidence of cancer increases every year, and is higher in the elderly population. Cancer treatment is an extremely complex process that requires different treatment modalities. The development of medicine and the acquisition of new knowledge in a field of cancer treatment has led to the development of immunotherapy as one of the fundamental modalities of treatment in addition to surgery, radiotherapy, and chemotherapy. Research studying the interaction of the immune system and tumors have led to the discovery of immune checkpoints as potential targets for drugs. This created the possibility of research and development of immune checkpoint inhibitors that changed the treatment paradigm in oncology. The introduction of immune checkpoint inhibitors into clinical practice has necessitated the development of biomarkers to identify patients who will potentially benefit from that therapy. Tumor mutational burden is a measure that quantifies the number of mutations per megabase that exists in a tumor. It has been shown to be a good predictor of response to immune checkpoint inhibitor therapy in certain tumor types. With the development of new generation sequencing, the cost and complexity of determining tumor mutational burden has been reduced, which enabled its application in the clinical environment. Although tumor mutational burden is approved for the use in the clinical setting, a number of new questions have been raised regarding its ability to predict response to immune checkpoint inhibitor therapy in different tumor types, as well as determining cut-off values for classification of tumors into those with high or low mutational load. By dividing patients based on TMB values, patients can be selected better for the treatment with immune checkpoint inhibitor therapy.