The RBL mast cell line was established in 1973. After its adaptation to in vitro culture and the establishment of a histamine-secreting subline (RBL-2H3), this cell line has been a preferential model in fundamental research on mast cells and in pharmacological studies that evaluate the capacity of antagonists to inhibit the degranulation response. Numerous advances on mast cell biology have been achieved using RBL cells. Notably, this model has enabled the precise biochemical characterisation of the high affinity interaction of the IgE molecule with its receptor (FcεRI). It has also allowed the biochemical description and molecular cloning of the α, β and γ subunits that compose the FcεRI as well as the cellular mechanisms initiated by the aggregation of receptor-bound IgE by an allergen. More recently, a model expressing the human FcεRI α chain has been obtained, which allows investigating human IgE functions, as this Ig isotype is species-specific and cannot bind to rodent receptors. It is likely that the RBL model will continue to serve for many years as a basic model system to study the biological properties of mast cells in both fundamental and clinical research applications.