1. To have no money; to be broke. The phrase was originally used to describe people who were so poor that they had worn their shoes down to the uppers (the part of the shoe above the sole). This usage includes a pronoun between "on" and "uppers," and can include "down" between "be" and "on." Primarily heard in UK. I am down on my uppers this week, so can we go out for dinner next week, after I get paid?

2. slang To be on stimulant drugs. In this usage, the set phrase is "be on uppers." My son has been acting really weird and says he's been awake for days, so I'm worried that he's on uppers.