Understanding the set of functions performed by the protein-coding genes of the human genome has been a longstanding goal of biomedical research. The last two decades has seen substantial progress towards achieving this goal, with continued improvements in the annotation of the human genome sequence, and dramatic advances in the experimental characterization of human genes and their homologs from well-studied model organisms. Here, we describe the first attempt to create a draft human "functionome" through a comprehensive synthesis of functional data obtained for human genes and their homologs in non-human model organisms. All relevant function information in the Gene Ontology knowledgebase has been synthesized using an evolutionary framework based on phylogenetic trees, creating curated models of function evolution for 6333 gene families. This allowed the association of at least one functional characteristic to 82% of human protein-coding genes, each of which can be individually traced to experimental evidence in human and/or non-human model systems. Our evolutionary models provide an insight into how functions have evolved over different time periods to build up the repertoire of human gene functions. The evolutionary models and resulting GO annotations are useful in numerous applications from gene set enrichment analysis to understanding genetic evolution.