Cell trafficking disorders (CTD) are genetic defects in complex molecules and correspond to the largest category of IEM with mutations in more than 370 genes described. They are still poorly recognized as a global entity but rather seen as isolated rare diseases by non-metabolic specialists. Complex lipid metabolism (mostly phospholipids, sphingolipids, and non-mitochondrial fatty acids) is tightly associated with cell trafficking and interactions between organelles at the membrane contact sites. Accordingly, from a clinical point of view CTD presents with multisystem manifestations that may overlap and mimic mitochondrial and other complex molecule disorders such as peroxisomal, lysosomal defects, CDG, or autophagy disorders. The nervous system is especially vulnerable and neurological presentations are prominent, but CTD targets any organ at any age. Interestingly the involvement of the immune system is particularly characteristic of CTD and rarely (or at least little described so far) in other categories of IEM. Most CTD are progressive disorders, except for CDG. They may have "metabolic crises" mimicking disorders of intermediary and energy metabolism for which emergency protocols have been developed. They are generally diagnosed by exome sequencing. Relatively few biomarkers are available.