The objective of this review is to provide a comprehensive summary of the latest methodological advancements and emerging patterns in utilizing lipidomics in clinical research.In this review, we assess the recent advancements in lipidomics methodologies that exhibit high levels of selectivity and sensitivity, capable of generating numerous molecular lipid species from limited quantities of biological matrices. The reviewed studies demonstrate that molecular lipid signatures offer new opportunities for precision medicine by providing sensitive diagnostic tools for disease prediction and monitoring. Moreover, the latest innovations in microsampling techniques have the potential to make a substantial contribution to clinical lipidomics. The review also shows that more work is needed to harmonize results across diverse lipidomics platforms and avoid significant errors in analysis and reporting. The increased implementation of internal standards and standard reference materials in analytical workflows will aid in this direction.