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The lipidome catalogue has more than 40,000 compounds, but the biological role of many of these is unknown. Our current understanding of protein–lipid interactions is largely based on biophysical or structural studies of a few prototypes, and there is a need for more generic approaches that can be scaled up to identify and characterise more interactions. This collection of articles includes step-by-step protocols published in Nature Protocols and related reviews published in Nature Reviews Molecular Cell Biology, which describe and discuss recently-developed technologies that enable protein-lipid interactions to be studied on a systems level.