Frank Costantini grew up in New York City, one of three sons. His father was a chemical engineer, his mother an artist. He was good in math and liked quantitative, objective subjects. He matriculated at Yale University, working on RNase Q in Sidney Altman's lab. For graduate school Costantini chose California Institute of Technology, in part because a girlfriend was going to University of California, Los Angeles. He entered Eric Davidson's lab to work on sea urchins; William Klein, a postdoc, acted as his submentor. The science in Davidson's lab was mostly biochemical and molecular, but Costantini thought it more important to know the "logic behind doing science" than what science the lab did. Costantini still wanted, however, to focus on molecular biology, especially as applied to mammals, so he went into Christopher Graham's lab at University of Oxford. His wife, Elizabeth Lacy, also did a postdoc in Graham's lab. There Costantini worked on deriving embryonic carcinoma cell lines to go into the germ line to make genetically altered mice. At first this did not work, but Costantini showed the possibility of getting into the germ line by injecting DNA directly into the nucleus of an egg, rather than into the cytoplasm. Then a new research field, his result has now become a commonly-used technique. Thinking about another postdoc, this time at Rockefeller University, Costantini was instead persuaded to apply for a job that had come open at Columbia University, and his wife took a job at Memorial Sloan Kettering Cancer Center. Although both are still working on mutations that affect early development, they no longer collaborate. At Columbia Costantini can do whatever he can get funding for. His lab is an exciting place, with much happening. He likes to figure out what can be done with a new and interesting technique rather than try to fit the technique to a specific project. He still works mostly on mammalian development biology and gene regulation. He says that embryonic stem (ES) cells can now enable mutations in all genes, and that his best collaboration is with Elizabeth Robertson and her ES cells work. Costantini concludes his interview by saying that his free time is dominated by his eighteen-month-old son. He also likes to cook and to travel when he can. He still loves the intellectual challenge of science.