Methylotrophic yeasts are unique eukaryotic organisms, that can metabolize toxic one-carbon substrate, methyl alcohol or methanol. About 50 species of methylotrophic yeasts is known, among them 4 species are the best studied: Pichia methanolica, Hansenula polymorpha, Pichia pastoris i Candida boidinii. These organisms, especially P. pastoris i H. polymorpha appeared to be very perspective overproducers of heterologous proteins and nowadays are used for industrial production of some of them. In this review, we provide information on the organization of the genome, mechanisms of regulation of gene expression and the use of strong promoters of these yeast species to construct the producers of heterologous proteins. In more details, we analyze genetic control of carbon and nitrogen catabolic repression in H. polymorpha and also the identification of metabolites inducing catabolite repression or peroxisome selective autophagy in the medium with ethanol in the Pichia methanolica yeast.