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Understanding the interaction between organisms and the environment is important for predicting and mitigating the effects of global phenomena such as climate change, and the fate, transport, and health effects of anthropogenic pollutants. By understanding organism and ecosystem responses to environmental stressors at the molecular level, mechanisms of toxicity and adaptation can be determined. This information has important implications in human and environmental health, engineering biotechnologies, and understanding the interaction between anthropogenic induced changes and the biosphere. One class of molecules with unique promise for environmental science are lipids; lipids are highly abundant and ubiquitous across nearly all organisms, and lipid profiles often change drastically in response to external stimuli. These changes allow organisms to maintain essential biological functions, for example, membrane fluidity, as they adapt to a changing climate and chemical environment. Lipidomics can help scientists understand the historical and present biofeedback processes in climate change and the biogeochemical processes affecting nutrient cycles. Lipids can also be used to understand how ecosystems respond to historical environmental changes with lipid signatures dating back to hundreds of millions of years, which can help predict similar changes in the future. In addition, lipids are direct targets of environmental stressors, for example, lipids are easily prone to oxidative damage, which occurs during exposure to most toxins. This is the first review to summarize the current efforts to comprehensively measure lipids to better understand the interaction between organisms and their environment. This review focuses on lipidomic applications in the arenas of environmental toxicology and exposure assessment, xenobiotic exposures and health (e.g., obesity), global climate change, and nutrient cycles. Moreover, this review summarizes the use of and the potential for lipidomics in engineering biotechnologies for the remediation of persistent compounds and biofuel production. With the preservation of certain lipids across millions of years and our ever-increasing understanding of their diverse biological roles, lipidomic-based approaches provide a unique utility to increase our understanding of the contemporary and historical interactions between organisms, ecosystems, and anthropogenically-induced environmental changes.