T cells recognizing lipid antigens are present in large numbers in circulating blood. They exert multiple functions including immunoregulation, tumour surveillance and protection during infection. Here, we review the latest information on the mechanisms of lipid antigen presentation by CD1 molecules. Recent studies have provided insight into CD1 trafficking within the cell, lipid distribution and handling, CD1 maturation, lipid antigen processing and loading. The structural resolution of all human CD1 molecules has revealed unique features that correlate with function. Molecular mechanisms regulating CD1 expression and multiple evasion mechanisms evolved by viral and bacterial pathogens have been disclosed. With rapid progression, these studies have decoded lipid-specific immunity and have revealed the important immunological role of this type of antigen recognition.