During the past 15 years, the methylotrophic yeast Pichia pastoris has proven to be an excellent host for the production of both secreted and intracellular proteins. Numerous heterologous proteins have been produced at greater than gram per liter levels using alcohol oxidase promoter. The increasing popularity of this particular expression system can be attributed to several factors, most importantly: the simplicity of techniques for genetic manipulation, the ability to produce foreign proteins at high levels and the capability to perform many posttranslational modifications. The factors that drastically influence protein expression in this system include: copy number of the expression cassette, site and model of chromosomal integration of the heterologous gene, mRNA sequence and secondary structure, transcriptional and translational blocks, nature of secretion signal, endogenous proteases, host strain physiology, media and growth conditions. In this paper, I review how the system was developed, how it works and what can be done about it in the future.