This chapter discusses the most recent findings on the reassignment mechanism of CUG codons from leucine to serine in various Candida and non-Candida species, the so-called CTG clade. It highlights how the Candida albicans model system improves one's understanding of the evolution of the genetic code, and explains how this genetic code alteration shaped the biology of the CTG clade species. Codon reassignments show that the genetic code evolves even in organisms with complex genomes and proteomes. The codon capture theory postulates that genetic code changes result from genome G+C biases on codon usage. There is significant flexibility in the genetic code to support codon reassignment. The phenotypic diversity induced by CUG ambiguity exposes some of these virulence traits, suggesting that CUG ambiguity may be relevant to pathogenesis and that C. albicans may have evolved unique mechanisms to take advantage of its genetic code alteration. The double identity of the CUG codon implies that each protein is represented by a mixture of molecules containing Leu or Ser at CUG positions. This creates a statistical proteome whose biological implications are still poorly understood. Nevertheless, the probability of finding identical cells in nature is extremely small.