SummaryGluconeogenesis, or the formation of glucose from mainly lactate/pyruvate, glycerol and alanine, plays an essential role in the maintenance of normoglycaemia during fasting. Inborn deficiencies are known of each of the four enzymes of the glycolytic — gluconeogenic pathway that ensure a unidirectional flux from pyruvate to glucose: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose‐1,6‐bisphosphatase, and glucose‐6‐phosphatase. In this paper, the clinical picture, pathophysiology, diagnostic tests, genetics, treatment and prognosis of the deficiencies of fructose‐1,6‐bisphosphatase and phosphoenolpyruvate carboxykinase are reviewed.