The Lipid Metabolites and Pathways Strategy (LIPID MAPS) initiative constitutes the first broad scale national exploration of lipidomics and is supported by a U.S. National Institute of General Medical Sciences Large Scale Collaborative "Glue" Grant. The emerging field of lipidomics faces many obstacles to become a true systems biology approach on par with the other "omics" disciplines. With a goal to overcome these hurdles, LIPID MAPS has been developing the necessary infrastructure and techniques to ensure success. This review introduces a few of the challenges and solutions implemented by LIPID MAPS. Among these solutions is the new comprehensive classification system for lipids, along with a recommended nomenclature and structural drawing representation. This classification system was developed by the International Lipids Classification and Nomenclature Committee (ILCNC) in collaboration with LIPID MAPS and representatives from Europe and Asia. The latest changes implemented by the committee are summarized. In addition, we discuss the adoption of mass spectrometry (MS) as the instrumental platform to investigate lipidomics. This platform has the versatility to quantify known individual lipid molecular species and search for novel lipids affecting biological systems.