Dendritic cells (DCs) play a key role in regulating innate and adaptive immunity. Our understanding of DC biology has benefited from studies in CD11c.DTR and CD11c.DOG mouse models that use the CD11c promoter to express a diphtheria toxin (DT) receptor transgene to inducibly deplete CD11c⁺ cells. Other models to inducibly deplete specific DC subsets upon administration of DT have also been generated. However, most models suffer from limitations such as depletion of additional cell types or the requirement to be used as radiation chimeras. Moreover, CD11c.DTR and CD11c.DOG mice have recently been reported to display neutrophilia and monocytosis upon DT injection. We discuss here some of the limitations that should be taken into consideration when interpreting results obtained with mouse models of DC ablation.