At the top of their list: the crisis in Ukraine.
Allied leaders have already indicated they will buttress their support for Kiev and bolster defences against Russia.
Secretary General Anders Rasmussen set the tone by accusing Moscow outright of attacking Ukraine.
Kiev wants to join the alliance, but that could create a rift within NATO.
Membership would oblige the other nations to defend Ukraine militarily, and that's not something the alliance says it wants to do.
US President Barack Obama says the door to new membership should remain open, but France and Germany are opposed to admitting Kiev.
The nearly 30 allied leaders will also discuss how to tackle the fundamentalist group, Islamic State, which has emerged as a new threat on the alliance's southern flank.
NATO diplomats say the alliance as a whole is unlikely to follow the US lead and stage military strikes on Islamic State, although over the two days of the summit all options are open for discussion.