Lithium stays a standard in first line treatment of bipolar disorder, a disease which includes depression accompanied by manic episodes. Considering the low therapeutic index of lithium and the risk of severe toxicity, lithium blood levels have to be monitored continuously during treatment. Serum and plasma are actually the main specimens used in laboratories for determination of lithium levels. Methods for Li determination are Flame Emission Photometry (FEP), Atomic Absorption Spectroscopy (AAS), Ion Selective Electrode (ISE) and colorimetry (CY). ISE and colorimetry methods are suitable to the ubiquitous clinical analyzers used in laboratories. In addition to serum and plasma, lithium levels determination in erythrocytes, its ratio with plasma levels and determination represent other interesting tools for evaluation of therapeutic response and toxicity. Accurate monitoring of lithium blood concentrations and complete evaluation of the method used for it required consideration of preanalytical factors such as specimens type and aspect, intra, and inter-individual variations. Analytical factors such as specificity, selectivity, linearity and total imprecision have also to be considered. The same as laboratories and laboratory techniques, lithium monitoring is in evolution. Indeed it could be integrated in laboratory solutions for analytical consolidation and could be realized by point of care testing, non-invasive assays like iontophoresis or 7Li MR method.