In recent years, there have been remarkable improvements in the treatment of hematological malignancies with the introduction of novel therapeutic modalities. The advent of these therapies has made it feasible to significantly and permanently decrease (possibly eradicate) tumor cells in the body. Evaluating the effectiveness of these treatments required the development of a new diagnostic method. Currently, the most appropriate approach for assessing the objective response is through the measurement of "measurable residual disease" (MRD). MRD refers to the presence of malignant cells in a patient's body after receiving treatment, even in the absence of apparent signs or symptoms. Several techniques can be employed to detect MRD, including multiparametric flow cytometry, RQ-PCR as well as more recent approaches including digital PCR or next generation sequencing. This review offers an in-depth overview of the different techniques used to estimate measurable residual disease and their current applications in hematological malignancies.