Typically, people will use them on flights operated by Delta to upgrade from economy to business class, although the airline's "E" basic economy class is excluded. Another option, although less valuable, is to use the Global Upgrade certificates on SkyTeam parters like Air France or KLM — with the caveat that you must be ticketed in the pricier Y, B or M fare classes.
Recently though, the policy changed to expand certificate eligibility on KLM codeshare flights (that were booked through Delta) to include a wider variety of eligible fare classes, notably more economy-level tickets — the eligible main cabin fare classes are: Y, B, M, S, H, Q, K, L, U, T, X and V.
If you're a Delta flyer traveling internationally, this is great news. While Delta's premium product is a solid option, more choices are always a good thing. Keep in mind that you must be on a Delta-marketed flight and that Global Upgrades on KLM flights must be confirmed 24 hours prior to departure — they also may not be used to waitlist these KLM-operated flights. Nonetheless, if you're headed to the Netherlands or any other destination KLM serves, this could be worth considering.
H/T: Rene's Points
