One-component systems (OCSs) and cytosolic two-component regulatory systems (TCSs) appear to share the same biological function, which consists in the transcriptional control in response to the cellular concentration of signal molecules. However, cytosolic TCSs as compared with OCSs represent a genetic and metabolic burden to the cell: the genetic information encoding a TCS is significantly larger than that of an OCS, two or more proteins instead of one need to be synthesized for a TCS and operation of the latter system requires the expense of ATP which is not the case for most OCSs. The evolutionary advantages of cytosolic TCSs over OCSs are thus not obvious. We hypothesize here that the increased capacity of cytosolic TCSs to respond to multiple signals is a major advantage over OCSs. Different mechanisms for the incorporation of additional signals into the regulatory circuit are discussed. The inclusion of several signals into the definition of the final regulatory response is proposed to result in a better adaptation of the host to given environmental conditions.