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I'm a big fan of Watsi. They fund life-changing medical treatments for people. They won't, say, pay for ongoing medication, but they'll pay for one-off surgeries and treatments that will immediately change lives. They were one of the first Y Combinator backed nonprofits. I also like the Center for Addiction and Mental Health, and Covenant House (youth homeless shelter). By total, Watsi gets the most money from me.