In Google's 2013 Founders' Letter, Larry Page described Calico as a company focused on health, well-being, and longevity. The company's name is an acronym for California Life Company.
In 2015, Google restructured into Alphabet Inc., making Calico a subsidiary of the new company and Google and others. As of 2018, Calico has not developed any known drugs or biotechnology products.
In September 2014, Calico announced that in partnership with AbbVie, Calico would be opening up an R&D facility focused on aging and age-related diseases, such as neurodegeneration and cancer. Initially, each company will invest $350 million, with an option for each to add an extra $500 million later on. In the same month, Calico announced a partnership with the University of Texas Southwestern Medical Center and 2M Companies regarding drug development for neurodegenerative disorders.
In 2015, the Broad Institute of MIT and Harvard announced a partnership with Calico to "advance research on age-related diseases and therapeutics." A further collaboration was also announced with the Buck Institute for Research on Aging. Also, in 2015, Calico announced a partnership with QB3 based on researching the biology of aging and identifying potential therapeutics for age-related diseases and one with AncestryDNA based on studying the genetics of human lifespan.
At the end of 2017 and the beginning of 2018, Calico lost two top scientists; in December 2017, Hal Barron, it's head of R&D, left for GlaxoSmithKline, and in March 2018, Daphne Koller, who was leading their AI efforts, left to pursue a venture in applying machine learning techniques to drug design.