Micellar liquid chromatography (MLC), which uses mobile phases of surfactants above the critical micellar concentration, provides a solution to the direct injection of physiological samples by solubilizing the protein components, and coating the analytical column with surfactant monomers to avoid clogging. A review showing the advantages and limitations of this technique over other chromatographic techniques used in drug analysis, working protocols, and examples of application is presented. The possibility of direct sample introduction simplifies and greatly expedites the treatments with reduced cost, improving the accuracy of the procedures. Surfactant monomers and micelles appear to displace drugs bound to proteins, releasing them for partitioning to the stationary phase. The versatility of MLC encompasses the wide range of drug classes normally monitored, such as analgesics, anticancer drugs, antidepressants, bacteriostats, beta-blockers, bronchodilators, catecholamines, diuretics and steroids, among others. Analytical procedures have been developed in urine, plasma, serum and cow milk samples. Most of them utilize sodium dodecyl sulphate as surfactant and a C18 column. UV detection is usual, but enhanced detection has been reported by measuring the absorbance in the visible region of drug derivatives formed precolumn, and with a variety of other techniques, such as fluorimetry, amperometry, inductively coupled plasma-mass spectrometry and immunoassay. Column-switching with on-line surfactant-mediated sample clean-up is shown as an attractive enrichment technique, which expands the practical use of MLC beyond the singular dimensional chromatographic process.