The production of food and feed, industrial proteins, and biopharmaceuticals requires cost-efficient protocols and rationally chosen heterologous production hosts. Among established production platforms, ranging from bacteria to mammalian cells, yeasts combine the advantages of unicellular organisms, such as fast biomass growth and relatively easy genetic manipulations, with eukaryotic features such as correct posttranslational modifications of recombinant proteins and an efficient secretory pathway. Simultaneously, unlike more complex eukaryotic organisms, yeast expression systems are more economical, and unlike bacterial hosts, they do not contain pyrogenic or viral inclusions. Yeasts also offer a high diversity of metabolic and physiological adaptations that can be exploited in biotechnology, including recombinant protein production. Herein, methylotrophic yeasts, mainly Pichia pastoris (syn. Komagataella phaffii) and Hansenula polymorpha (syn. Ogataea polymorpha) (in this review, the traditional nomenclature of yeast species is used), are overviewed as alternative expression platforms for the production of heterologous proteins such as industrial enzymes and biopharmaceuticals.