It's a bitter blow to both player and team. At the age of 28, it could be Falcao's last chance to be the nation's star player at a World Cup, but it's a chance he will not get. It also severely hinders Colombia's odds of making a deep run in the tournament.
Colombia still figures to be a favorite to make it out of Group C given the lack of traditional powers in the group. The South American country shouldn't need Falcao to get past Greece, Japan and the Ivory Coast, but contributions from the former Atletico Madrid striker would have greatly aided the chances of Colombia making a deep run in the tournament.
Falcao's absence places additional pressure on Colombia's current stable of strikers to produce the goods up front.
Teofilo Gutierrez, Adrian Ramos and Jackson Martinez figure to be the key players up front while James Rodriguez and Fredy Guarin will provide support in the midfield.
Gutierrez was Colombia's second-highest scorer in CONMEBOL qualifying as his total of six goals was three fewer than Falcao's output.
Ramos, who recently completed a move to Borussia Dortmund, and Martinez of FC Porto are accomplished players on the club side of football but have combined to score just 10 goals in 51 appearances for the national team. They will need to shoulder some of the scoring burden to assist Gutierrez.
Rodriguez is one of the players that is surely most disappointed by Falcao's absence from the squad. The duo exhibited their chemistry all season at Monaco, and the prospect of the two combining for Colombia at the World Cup was a tantalizing prospect. But Rodriguez is a promising player who will be eager to show what he can do on the biggest stage, even without his running mate.
Guarin, meanwhile, is a bit more inconsistent. The 27-year-old Inter Milan attacker can show bits of brilliance but has also shown a tenancy to fade away in crucial spots. He will need to be at his best if Colombia harbors hopes of making a deep run in Brazil.
Colombia's defensive unit is quite established with the likes of Mario Yepes, Cristian Zapata, Pablo Amero and Juan Camilo Zuniga, but the nation's depth at the back is a little suspect. If head coach Jose Peckerman is forced to shuffle the back line due to suspensions or injuries, it could become Colombia's Achilles heel.
While there are a few concerns amid Falcao's absence, the Colombians have the talent to emerge from a relatively weak Group C. But how far they can advance beyond the group stages is anyone's guess.