Mevalonate kinase deficiency is a rare autosomal recessive inborn error of metabolism with an autoinflammatory phenotype. In this review we discuss its pathogenesis, clinical presentation and treatment. Mutations in both copies of the MVK-gene lead to a block in the mevalonate pathway. Interleukin-1beta mediates the inflammatory phenotype. Shortage of a non-sterol isoprenoid product of the mevalonate pathway, Geranylgeranylpyrophosphate leads to aberrant activation of the small GTPase Rac1, and inflammasome activation. The clinical phenotype ranges widely, depending on the severity of the enzyme defect. All patients show recurrent fevers, lymphadenopathy and high acute phase proteins. Severely affected patients have antenatal disease onset, dysmorphic features, growth retardation, cognitive impairment and progressive ataxia. Diagnosis relies on mutation analysis of the MVK-gene. There is no evidence based therapy. IL-1 blockade is usually effective. Severe cases require allogeneic stem cell transplantation. Targeted therapies are needed.