the agonists used here are mediated by the calcineurin–NFAT pathway rather than the MAPK pathway.” In my opinion, this comment crystallizes the dangers that Molkentin et al14 have unintentionally created, and I am convinced that the issue is far from settled. There are 3 main points that I wish to cover. First, is there evidence for the involvement of other (possibly interacting) signaling pathways leading to hypertrophy? Second, how convincing is the evidence for involvement of calcineurin? Third, if calcineurin is involved, how convincing is the mechanism proposed by Molkentin et al, 14 namely dephosphorylation of the transcription factor nuclear factor of activated T-lymphocytes-3 (NFAT3)?