Inteins, the polycatalytic mobile genetic elements of the microbial world, are co-translated as intervening regions within essential host proteins. Protein splicing activity of the intein is necessary to bring the host protein to a fully active state. Due to their additional mobility at the DNA level, inteins have long been characterized as a class of selfish genetic sequences. In some cases, however, inteins appear capable of functioning adaptively as environmentally responsive posttranslational regulatory elements. In this chapter, we discuss some recent breakthroughs in the developing field of conditional protein splicing (CPS), whereby the rate and accuracy of intein activity are functionally linked to intra- and extracellular conditions. We highlight examples of inteins acting both as “pause buttons” and “rheostats” to provide an underappreciated means of posttranslational regulation. Lastly, we discuss evidence for an evolutionary link between CPS and the autoprocessing activity of eukaryotic hedgehog family proteins. Hedgehog autoprocessing yields a vital extracellular signaling factor with potent morphogenic activity. The close mechanistic parallels and structural similarities between intein splicing and hedgehog autoprocessing support speculation that an intein was exapted to catalyze a vital transformation for animal development.