The Rocky Mountain state made drug history on New Year's Day with the inauguration of retail sales of marijuana for recreational use.
The Pacific Northwest state of Washington is set to follow suit later this year -- even though, under federal law, marijuana remains as illegal and addictive as heroin, ecstasy and LSD.
In the immediate future, the main focus will likely be on the regulated sale of cannabis for medicinal use, which is already legal in 20 states, said John Hudak of the Brookings Institution think tank.
"Beyond that, I think most states are going to let the experiment in Colorado and Washington play itself out before they take the next steps forward" on recreational marijuana, Hudak told AFP.
In Alaska, campaigners are "very hopeful" of putting legalization to a popular vote in August, said Mason Tvert, communications director of the Marijuana Policy Project, a pro-pot lobby group in Washington.
Not so far advanced, but underfoot nevertheless, are similar efforts in Arizona, California, Maine, Massachusetts, Montana, Nevada and Oregon.
Taking another tack, campaigners are looking to state legislatures in Delaware, Hawaii, Maryland, New Hampshire, Rhode Island and Vermont to adopt laws allowing the retail sale of weed.
"Support for ending marijuana prohibition is at an all-time high nationwide, and we expect to see that (continue) to grow," Tvert said.
In October, for the first time in a Gallup poll, a majority of Americans -- 58 percent -- said they favored the legalization of marijuana.
Another survey, from the federal government's National Institute on Drug Abuse, found that 39.5 percent of US high school seniors viewed marijuana as harmful -- down from 44.1 percent a year ago.
With public opinion shifting, President Barack Obama's administration told federal prosecutors in August to no longer target individual marijuana smokers in states where legalization is in place.
While the trend appears to be leaning toward greater legalization, opponents say the risks of marijuana remain genuine.
"I definitely don't think it's a lost fight to work against legalization," said Kevin Sabet, a former White House drug policy adviser who is executive director of Smart Approaches to Marijuana.
SAM was initiated a year ago by former congressman Patrick Kennedy, a scion of the Kennedy political dynasty who has wrestled in the past with alcohol and prescription drugs.
Legalizing pot will prompt the rise of a Big Marijuana industry similar to the Big Tobacco corporations that for years resisted the regulation of cancer-causing cigarettes, Sabet told AFP.
Indeed, stocks of publicly-listed companies involved in the marijuana industry -- medical or otherwise -- hit fresh highs Thursday, as investors rushed into what could turn out to be a $10 billion-a-year business by 2018, according to some estimates.
"This movement (toward legalization) is not about hippies who want to smoke a joint once a month," Sabet said.
"This is about creating a major industry that starts with marijuana and moves on to other drugs -- and I really think people are going to wake up and see that soon."
Law enforcement agencies have also voiced concern, with the International Association of Chiefs of Police warning of a potential upsurge in fatal traffic accidents due to "drugged driving."