Pathway engineering in medicinal plants attains a special significance in Digitalis species, the main industrial source of cardiac glycosides, steroidal metabolites derived from mevalonic acid via the triterpenoid pathway. In this work, the Arabidopsis thaliana HMG1 cDNA, coding the catalytic domain of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR1S), a key enzyme of the MVA pathway, was expressed in the cardenolide-producing plant Digitalis minor. Transgenic plants were morphologically indistinguishable from control wild plants and displayed the same developmental pattern. Constitutive expression of HMG1 resulted in an increased sterol and cardenolide production in both in vitro- and greenhouse-grown plants. This work demonstrates that transgenic D. minor plants are a valuable system to study and achieve metabolic engineering of the cardenolide pathway and in consequence for the genetic improvement of Digitalis species.