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The controlled uptake and release of lipid compounds is a hallmark feature of living cells. Numerous factors have been implicated in these complex transmembrane transport processes. The recent discovery of a novel class of transporter molecules, the group of A-subclass ATP-binding cassette (ABC) transporters, has brought new insights into the molecular basis of cellular lipid transport. Available evidence indicates that individual ABC A-subclass transporters function as key components of highly specialized cellular lipid export machineries in major physiological systems and, when defective, cause hereditary diseases in the cardiovascular, respiratory, visual and integumentary systems, respectively. Intriguingly, a steadily growing body of evidence suggests that ABC A lipid transporters play important roles in the pathogenesis of complex disorders with high incidence including atherosclerosis, Alzheimer's disease and age-related macula degeneration. The present article reviews the biology of this emerging group of proteins and their implication in human pathologies.