The main differences between lipids and other biomolecules (carbohydrates, proteins and nucleic acids) are their solubility in non-polar solvents and structure of long hydrocarbon chains. Based on the physical and chemical properties, eukaryotic and prokaryotic lipids are grouped under eight categories, each of which contains distinct classes, subclasses, subgroups and subsets of lipid molecules. When studying lipids from a system scale, one of the key challenges is to address the lipid functionality at many physiological levels from metabolism, signaling pathways to spatial regulation, as well as the interactions with other “Omics”. Lipidomics is to map the entire spectrum of cellular lipids in biological systems, including metabolic pathways, lipid–lipid and lipid-protein interactions. It complements proteomics, genomics and metabolomics for providing a more comprehensive understanding of system biology in health and disease.