And the latest issues brought the tension to the surface.
The major concern for Lebanon is that Syria's troubles will reopen the wounds of Lebanon's 15-year-long civil war, which ended in 1990.
Aside from its southern border with Israel, Lebanon is entirely surrounded by Syria, and was considered part of "greater Syria" until the end of World War I.
It became an independent country in 1943 but has been strongly influenced by Syria both politically and militarily for much of the time since.
Syrian troops were deployed in Lebanon between 1976 and 2005, primarily in the north -- ostensibly at first as peacekeepers to help stop Lebanon's long civil war -- but maintained a significant presence long after the fighting stopped in 1990.
This all changed in 2005 after former Prime Minister Rafik Hariri was killed by a car bomb in Beirut.
Anti-al-Assad elements in Lebanon accused the Syrian government of being behind the attack, and popular protests -- along with international pressure -- forced the Syrian military to withdraw from the country.
Since then, Lebanon's two most prominent political blocs have been sharply divided in their attitude toward Syria: the ruling pro-Syria alliance led by Mikati and a group of anti-Syrian factions led by Saad Hariri, son of the assassinated former prime minister.
In addition, thousands of refugees have poured into Lebanon since the conflict in Syria began.
In this climate, any instability in Lebanese politics can only exacerbate the spillover from the Syrian war.
"Now it is important for dialogue to begin for a salvation government to be established during this difficult period," Mikati tweeted after submitting his resignation.
United Nations Secretary General Ban Ki-moon also called on cooler heads to prevail.
"At this challenging time for the region, the secretary-general calls on all the parties in Lebanon to remain united behind the leadership of President (Michel) Sleiman," a statement from his office said.