The qualified teams will be divided into two pools: those that won their groups, and those that progressed in second spot. As per usual, the eight seeded sides will play away in their respective first legs.
In addition, for the round of 16, no team can be drawn against a club from their own country or league, meaning that there is no chance of Group A winners Arsenal being paired with Group C runners-up Manchester City.
As it stands ahead of Wednesday's final round of games, there are still two qualification berths up for grabs.
Leicester City have secured top spot in Group G but FC Copenhagen and Porto are still battling it out for second place, with the latter side knowing that a win over the Foxes at the Dragao will seal their place in the last 16.
Meanwhile, in Group H, Juventus are through to the knockout phase but whether they will progress as seeds has yet to be determined, with second-placed Sevilla still in a position to overhaul the Bianconeri.
However, the Liga side's primary concern will be on avoiding a two-goal defeat in Lyon that would deny them qualification.
Elsewhere, the small matter of top spot will be at stake when Real Madrid host Group F leaders Borussia Dortmund at the Santiago Bernabeu. The reigning champions know that nothing less than victory will be enough to see them overhaul BVB, who have arrived in the Spanish capital with the cushion of a two-point advantage.
CHAMPIONS LEAGUE LAST 16 DRAW AS IT STANDS