The number of known human genes whose heterozygous null alleles lead to disease (i.e. haploinsufficient genes) is increasing. A recent update shows that they encode preferentially structural proteins, transcription regulators, signal transduction elements and various binding factors [1]. Surprisingly, in yeast, there are numerous haploinsufficient genes. Thus, in cases where there is a 50% reduction in gene activity, it is apparent that the old assertion that most mutations are recessive [2] does not hold.