The red cell membrane is one of the best known membranes in terms of structure, function and genetic disorders. As any plasma membrane it mediates transport functions. It also provides the erythrocytes with their resilience and deformability. Many of the proteins and the genes performing these functions are known in great detail, although some disease-responsible genes are yet to be elucidated. Basic knowledge has shed light on important groups of genetic disorders. The latter include (i) the disorders of the red cell mechanics: hereditary spherocytosis, hereditary elliptocytosis and poikilocytosis, and (ii) the disorders of the passive flux of the monovalent cations across the membrane: the stomacytoses and allied conditions. Reciprocally, many information have come from genetics abnormalities. We will review the mutation-disease relationship. A number of points will be underscored: widespread weak alleles modulate the expression of the SPTA1 gene, encoding the alpha-chain of spectrin; mutations in the anion exchanger can give rise to an array of distinct nosological entities, including a renal condition; splenectomy is banned in the stomatocytoses; a variety of stomatocyosis is part of a pleiotropic syndrome that may includes perinatal fetal liquid effusions. The diagnosis, follow-up and treatment of the involved diseases have gradually improved.