Recent developments in instrumentation, ion beams or analyzers, for cluster time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging are described here. The methods which are employed to increase the sensitivity or to perform three-dimensional analyses in the organic materials are also illustrated. This review shows the improvements made for lipid imaging by cluster TOF-SIMS in various types of material and applications, and gives reasons for the expansion of its utilization. © 2013 Wiley Periodicals, Inc. Mass Spec Rev 33: 442-451, 2014.